CN112557302A - Multi-wavelength photoacoustic imaging method, driving system and experimental device - Google Patents

Abstract

The present application provides a multi-wavelength photoacoustic imaging method, driving system and experimental device, by using a single-wavelength pulsed laser source to excite a photoacoustic signal; using one or more continuous laser sources of different wavelengths to heat the imaging target, so that the The excited photoacoustic signals are enhanced to different degrees to realize multi-wavelength photoacoustic imaging. The pulsed laser source used for exciting the photoacoustic signal in the present application can realize pulse modulation and continuous modulation, is suitable for both time domain and frequency domain photoacoustic imaging, and has low cost.

Description

Multi-wavelength photoacoustic imaging method, driving system and experimental device

technical field

The invention relates to the technical field of multi-wavelength photoacoustic imaging, in particular to a multi-wavelength photoacoustic imaging method, a driving system and an experimental device.

Background technique

In recent years, photoacoustic imaging has attracted increasing research interest due to its unique advantages of combining light and sound. Utilizing high ultrasound spatial resolution and optical absorption contrast to achieve deep tissue imaging, photoacoustic imaging has been applied to various application scenarios, including anatomical, functional, and molecular imaging. However, the bulky and expensive laser source is one of the key bottlenecks that needs to be addressed for further compact system development. Photoacoustic imaging systems based on low-cost laser diodes (LDs) are one of the more promising solutions. In the field of photoacoustics, the laser source for inducing photoacoustic signals has two modulation modes, one is nanosecond short pulse modulation, and the other is swept-frequency sinusoidal continuous modulation. However, these two modulation modes are independent of each other, and the required laser sources are also independent of each other.

In conventional laser sources, pulsed laser sources and continuous laser sources are independent of each other. The two cannot be used interchangeably. Moreover, in photoacoustic imaging, although the traditional pulsed laser source has high energy, it is bulky, expensive, and has low repetition frequency, which is not conducive to the commercialization of photoacoustic imaging systems. For the swept frequency modulation of continuous laser, the traditional method is to combine a continuous laser source and a photoacoustic modulator. This approach requires additional cost of the photoacoustic modulator. In addition, the disadvantage of the traditional multi-wavelength photoacoustic imaging system is that it consists of multiple pulsed lasers with different wavelengths or an expensive pulsed laser with adjustable wavelengths.

Therefore, there is a need for a low-cost laser driving scheme or device that can achieve both pulse modulation and continuous modulation.

SUMMARY OF THE INVENTION

In view of the above-mentioned shortcomings of the prior art, the purpose of the present application is to provide a multi-wavelength photoacoustic imaging method, a driving system and an experimental device to solve the problems in the prior art.

In order to achieve the above purpose and other related purposes, the present application provides a multi-wavelength photoacoustic imaging method, the method includes: using a pulsed laser source of a single wavelength to excite a photoacoustic signal; using one or more continuous laser sources of different wavelengths to heat The imaging target can enhance the excited photoacoustic signal to different degrees, so as to realize multi-wavelength photoacoustic imaging.

In an embodiment of the present application, the photoacoustic signal is represented as: p ₀ (λ _i )=Γ ₀ η _th μ _a (λ _i )F _pulse , i=1, 2, 3...,; wherein , λ _i is the laser source wavelength, η _th is the conversion constant from optical absorption to heat, μ _a (λ _i ) is the optical absorption coefficient at wavelength λ _i , F _pulse is the pulsed optical flux assumed to be constant, Γ ₀ is the Grunesen parameter related to the local temperature.

其中，公式中的非线性效应项表示加热后所述格鲁奈森参数的增强部分；b是从加热到所述格鲁奈森参数变化的吸收热能的系数，τ_th是样品的热扩散率，F_CW是连续激光源的光通量，Δt是连续激光源照射的持续时间。In an embodiment of the present application, the enhanced photoacoustic signal is expressed as:

Among them, the nonlinear effect term in the formula represents the enhanced part of the Gruneisen parameter after heating; b is the coefficient of absorbed thermal energy from heating to the change of the Gruneisen parameter, and τ _th is the thermal diffusivity of the sample , F _CW is the luminous flux of the CW laser source, and Δt is the duration of the CW laser source irradiation.

In order to achieve the above object and other related objects, the present application provides a multi-wavelength photoacoustic imaging driving system, the driving system includes: a pulsed laser and a plurality of continuous lasers; wherein, the pulsed laser includes a dual-mode laser driver and a laser A diode, the pulsed laser is used to provide a pulsed laser source to excite the photoacoustic signal; the continuous laser is used to provide a plurality of continuous laser sources of different wavelengths to heat the imaging target.

In an embodiment of the present application, the dual-mode laser driver includes: an operational amplifier, a transistor, and a transient voltage suppressor; the operational amplifier includes: a first signal input terminal for inputting a trigger signal, coupled with a resistor The second signal input end of the laser diode, and the signal output end coupled with an adjustable resistance between the transistor and the transistor; the transient voltage suppressor is used to protect the laser diode from forward transient high voltage and reverse bias voltage of destruction.

In an embodiment of the present application, the pulsed laser has a single wavelength, and the wavelengths of the continuous lasers are different.

In order to achieve the above purpose and other related purposes, the present application provides a multi-wavelength photoacoustic imaging experimental device, the experimental device includes: the multi-wavelength photoacoustic imaging drive system described above, a PC terminal, an ultrasonic transducer, a pulse generator receiver, oscilloscope, stepping motor, and function generator; the PC terminal is used to drive the pulsed laser source and the continuous laser source in a specific order; the ultrasonic transducer is used to receive the multi-wavelength photoacoustic the photoacoustic signal excited by the imaging system; the pulse generator receiver for further amplifying the photoacoustic signal; the oscilloscope for collecting and amplifying the photoacoustic signal and transmitting it to the PC terminal, For the PC terminal to control the stepping motor to move the laser source.

In an embodiment of the present application, the specific sequence of driving the pulsed laser light source and the continuous laser light source is: pulsed laser light source-continuous laser light source-pulsed laser light source.

In an embodiment of the present application, the second pulse laser source in the specific sequence is triggered by the falling edge of the continuous laser diode driver in the multi-wavelength photoacoustic imaging driving system to excite the second pulse laser source. photoacoustic signal.

In summary, a multi-wavelength photoacoustic imaging method, driving system and experimental device of the present application use a single-wavelength pulsed laser source to excite a photoacoustic signal; use one or more continuous laser sources of different wavelengths to heat imaging The goal is to enhance the excitation of the photoacoustic signal to different degrees to achieve multi-wavelength photoacoustic imaging.

Has the following beneficial effects:

It can realize pulse modulation and continuous modulation at the same time, is suitable for both time domain and frequency domain photoacoustic imaging, and has low cost.

Description of drawings

FIG. 1 is a schematic flowchart of a multi-wavelength photoacoustic imaging method according to an embodiment of the present application.

FIG. 2 is a schematic structural diagram of a multi-wavelength photoacoustic imaging driving system in an embodiment of the present application.

FIG. 3 is a schematic circuit diagram of a dual-mode laser according to an embodiment of the present application.

FIG. 4 is a schematic diagram of waveforms of the CW laser diode current and the waveform changes of the corresponding CW lasers in different sinusoidal modulation frequencies in an embodiment of the present application.

FIG. 5 is a schematic structural diagram of a multi-wavelength photoacoustic imaging experimental apparatus in an embodiment of the present application.

FIG. 6 is a schematic diagram of a scene of a multi-wavelength photoacoustic imaging experimental device in an embodiment of the present application.

FIG. 7 is a schematic diagram of a scene of an experimental apparatus for phantom imaging according to an embodiment of the present application.

FIG. 8 is a schematic diagram of a scene of an experimental apparatus for in vivo mouse ear imaging according to an embodiment of the present application.

FIG. 9A is a schematic diagram showing the waveform of the time-domain acousto-optic signal amplitude with a laser pulse width of 40 ns in an embodiment of the present application.

FIG. 9B is a schematic diagram of waveforms of time-domain acousto-optic signal amplitudes with a laser pulse width of 100 ns in an embodiment of the present application.

FIG. 9C shows a schematic waveform diagram of the amplitude of the time-domain acousto-optic signal with a laser pulse width of 200 ns in an embodiment of the present application.

FIG. 10 is a schematic diagram showing imaging results of time-domain acousto-optic signals with different laser pulse widths in an embodiment of the present application.

FIG. 11A is a schematic diagram showing the waveform of the original noise before applying the matched filter in an embodiment of the present application.

FIG. 11B shows a schematic waveform diagram of the photoacoustic signal before applying the matched filter in an embodiment of the present application.

FIG. 11C is a schematic diagram showing the waveform of the original noise after applying the matched filter in an embodiment of the present application.

FIG. 11D shows a schematic waveform diagram of a photoacoustic signal after applying a matched filter in an embodiment of the present application.

FIG. 11E is a schematic diagram showing the frequency domain photoacoustic imaging results of three silicon tubes in an embodiment of the present application.

FIG. 12 is a schematic diagram showing the comparison of the imaging results of the mouse ear in an embodiment of the present application.

FIG. 13 is a schematic diagram showing waveforms of light absorption spectra of three color inks according to an embodiment of the present application.

FIG. 14A is a schematic diagram of waveforms showing the variation of the maximum allowable exposure amount with the exposure duration in an embodiment of the present application.

FIG. 14B is a schematic diagram of waveforms of acousto-optic signals generated by different heating durations and energies in an embodiment of the present application.

15A is a columnar schematic diagram showing the change of the photoacoustic signal amplitude of the red ink before and after heating with different wavelengths of continuous lasers according to an embodiment of the present application.

FIG. 15B is a columnar schematic diagram showing the changes of the acousto-optic signal amplitudes of three different color inks before and after heating with a 520 nm continuous laser in an embodiment of the present application.

FIG. 16 is a schematic diagram showing the comparison of photoacoustic signal imaging results of three color inks according to an embodiment of the present application.

FIG. 17A shows a waveform diagram of the relative change of the photoacoustic signal with respect to different preset red ink concentrations after 520 nm and 638 nm continuous laser heating in an embodiment of the present application.

FIG. 17B is a schematic diagram of waveforms of photoacoustic measurement results and calibration results in an embodiment of the present application.

Detailed ways

The embodiments of the present application are described below through specific specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the contents disclosed in this specification. The present application can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present application. It should be noted that the embodiments in the present application and the features of the embodiments may be combined with each other under the condition of no conflict.

The embodiments of the present application will be described in detail below with reference to the accompanying drawings, so that those skilled in the art to which the present application pertains can easily implement. The present application can be embodied in many different forms, and is not limited to the embodiments described herein.

In order to clearly describe the present application, components irrelevant to the description are omitted, and the same reference numerals are given to the same or similar components throughout the specification.

Throughout the specification, when a component is said to be "connected" to another component, this includes not only the case of "direct connection" but also the case of "indirect connection" with other elements interposed therebetween. In addition, when a certain member is said to "include" a certain constituent element, unless there is particularly no description to the contrary, it does not exclude other constituent elements, but means that other constituent elements may also be included.

When an element is said to be "on" another element, it can be directly on the other element, but it can also be accompanied by other elements in between. When an element is referred to as being "directly on" another element, it is not accompanied by the other element in between.

Although in some instances the terms first, second, etc. are used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, the first interface and the second interface are described. Also, as used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context dictates otherwise. It should be further understood that the terms "comprising", "comprising" indicate the presence of stated features, steps, operations, elements, components, items, kinds, and/or groups, but do not exclude one or more other features, steps, operations, The existence, appearance or addition of elements, assemblies, items, categories, and/or groups. The terms "or" and "and/or" as used herein are to be construed to be inclusive or to mean any one or any combination. Thus, "A, B or C" or "A, B and/or C" means "any of the following: A; B; C; A and B; A and C; B and C; A, B and C" . Exceptions to this definition arise only when combinations of elements, functions, steps, or operations are inherently mutually exclusive in some way.

The technical terms used herein are only used to refer to specific embodiments and are not intended to limit the application. The singular form used here also includes the plural form, as long as the sentence does not clearly express the opposite meaning. The meaning of "comprising" as used in the specification is to embody particular characteristics, regions, integers, steps, operations, elements and/or components, but not to exclude other characteristics, regions, integers, steps, operations, elements and/or components exist or append.

The relative spatial terms "lower," "upper," etc. may be used to more easily describe the relationship of one element to another element as illustrated in the figures. Such terms refer not only to the meaning indicated in the drawings, but also to other meanings or operations of the device in use. For example, if the device in the figures is turned over, elements described as "below" other elements would then be described as "on" the other elements. Thus, the exemplary term "below" includes both above and below. The device may be rotated through 90° or other angles, and terms representing relative space are to be interpreted accordingly.

The photoacoustic imaging (PAI) is a new non-invasive and non-ionizing biomedical imaging method developed in recent years. When the pulsed laser is irradiated (thermoacoustic imaging refers specifically to the irradiation of radio frequency pulsed laser) into the biological tissue, the light absorption domain of the tissue will generate an ultrasonic signal, which we call photoacoustic. Signal. The photoacoustic signal generated by biological tissue carries the light absorption characteristic information of the tissue, and the light absorption distribution image in the tissue can be reconstructed by detecting the photoacoustic signal. Photoacoustic imaging combines the advantages of high selectivity in pure optical tissue imaging and deep penetration in pure ultrasound tissue imaging, and can obtain high-resolution and high-contrast tissue images, avoiding the influence of light scattering in principle, breaking through the High-resolution optical imaging depth "soft limit" (~1mm), enabling deep in vivo tissue imaging of 50mm.

In photoacoustic imaging, although the traditional pulsed laser source has high energy, it is bulky, expensive, and has low repetition frequency, which is not conducive to the commercialization of photoacoustic imaging systems. For the swept frequency modulation of continuous laser, the traditional method is to combine a continuous laser source and a photoacoustic modulator. This approach requires additional cost of the photoacoustic modulator. In addition, consider that the traditional multi-wavelength photoacoustic imaging system is composed of multiple pulsed lasers with different wavelengths or an expensive pulsed laser with adjustable wavelengths.

Therefore, the present application proposes a multi-wavelength photoacoustic imaging method, driving system and experimental device that can simultaneously realize pulse modulation and continuous modulation, and realizes a multi-wavelength photoacoustic imaging system by combining multiple continuous laser diodes with different wavelengths.

As shown in FIG. 1 , a schematic flowchart of a multi-wavelength photoacoustic imaging method in an embodiment of the present application is shown. Wherein, the method described in this application is applicable to the driving system described in this application. As shown, the method includes:

Step S101 : using a pulsed laser source with a single wavelength to excite the photoacoustic signal.

The photoacoustic signal is usually excited by a pulsed laser, and the photoacoustic signal is correspondingly expressed as:

p ₀ (λ _i )=Γ ₀ η _th μ _a (λ _i )F _pulse ,i=1,2,3...,,;

where λ _i is the laser source wavelength, η _th is the conversion constant from optical absorption to heat, μ _a (λ _i ) is the optical absorption coefficient at wavelength λ _i , F _pulse is the pulsed optical flux assumed to be constant, Γ ₀ is the Grunesen parameter related to the local temperature.

Step S102 : using one or more continuous laser sources with different wavelengths to heat the imaging target, so as to enhance the excited photoacoustic signals to different degrees, so as to realize multi-wavelength photoacoustic imaging.

In this embodiment, by heating the local tissue to change the local temperature, the Gruneisen parameter will increase nonlinearly, which will further excite stronger photoacoustic signals. At the same time, heating with different wavelengths of laser light will result in different increments of the excited photoacoustic signal due to the apparent light absorption of the tissue at different wavelengths. Therefore, multi-wavelength photoacoustic imaging can be achieved by combining a pulsed laser source and several continuous laser sources of different wavelengths.

In detail, the photoacoustic signal enhanced after heating by a continuous laser source at wavelength _λi is expressed as:

Among them, the nonlinear effect term in the formula represents the enhanced part of the Gruneisen parameter after heating; b is the coefficient of absorbed thermal energy from heating to the change of the Gruneisen parameter, and τ _th is the thermal diffusivity of the sample , F _CW is the luminous flux of the CW laser source, and Δt is the duration of the CW laser source irradiation.

In addition, the relative change of the photoacoustic signal relative to the signal without heating can be written as:

It is obvious that Δp(λ _i ) is linearly proportional to μ _a (λ _i ) of the sample to the CW laser, and other variables are independent of wavelength, indicating that the proposed method is based on nonlinear incremental partial extraction of optical absorption properties. The above expression is further simplified to:

Δp(λ _i )=Γ _n μ _a (λ _i )F _CW ,; where,

In one or more practical embodiments, the pulsed laser may be fixed at a wavelength of 450 nm for a duration of 200 ns. The multi-wavelength CW laser diode module can be constructed by simply integrating several CW laser diode drivers to drive each laser diode of different wavelengths, thus achieving 450nm, 520nm, 638nm, 650nm, 808nm and 1064nm. Their maximum adjustable power is 1W, 0.7W, 1W, 1W, 0.4W, 2W and 3W respectively.

As shown in FIG. 2 , a schematic structural diagram of a multi-wavelength photoacoustic imaging driving system in an embodiment of the present application is shown. As shown in the figure, the multi-wavelength photoacoustic imaging driving system 200 includes:

a pulsed laser 210, and a plurality of continuous lasers 220;

The pulsed laser 210 includes a dual-mode laser driver 221 and a laser diode 222. The pulsed laser 210 is used to provide a pulsed laser source to excite a photoacoustic signal; the continuous laser 220 is used to provide a plurality of continuous lasers with different wavelengths. source to heat the imaging target.

In some embodiments, the number of the CW lasers 220 in the multi-wavelength photoacoustic imaging driving system 200 may be one or more, and one is taken as an example in FIG. 2 .

Usually laser modulation is the process of using laser as a carrier for modulation. Laser has excellent temporal coherence and spatial coherence. It is similar to radio waves, easy to modulate, and the frequency of light waves is extremely high, which can transmit information with a large capacity. In addition, the divergence angle of the laser beam is small, and the light energy is highly concentrated, which can transmit a long distance and is easy to keep secret.

In the field of photoacoustics, the laser source for inducing photoacoustic signals has two modulation modes, one is nanosecond short pulse modulation, and the other is swept-frequency sinusoidal continuous modulation.

The pulse working mode of the pulsed laser source refers to a light pulse emitted by the laser at a certain interval. Pulse lasers have large output power and are suitable for laser marking, cutting, ranging, etc. It is necessary to work with pulses, such as sending signals and reducing heat generation. Laser pulses can be made extremely short, such as in the "picosecond" level, meaning that the pulse duration is on the order of a picosecond - and a picosecond is equal to one trillionth of a trillion.

A continuous laser source refers to a continuous laser source that can continuously provide energy and generate laser output for a long time. The output power of continuous lasers is generally relatively low, which is suitable for occasions requiring continuous laser operation (such as laser communication, laser surgery, etc.).

However, these two modulation modes are independent of each other, and the required laser sources are also independent of each other, so they cannot be used interchangeably. Moreover, in photoacoustic imaging, although the traditional pulsed laser source has high energy, it is bulky, expensive, and has low repetition frequency, which is not conducive to the commercialization of photoacoustic imaging systems. For the swept frequency modulation of continuous laser, the traditional method is to combine a continuous laser source and a photoacoustic modulator. This approach requires additional cost of the photoacoustic modulator. In addition, conventional multi-wavelength photoacoustic imaging systems are composed of multiple pulsed lasers with different wavelengths or an expensive pulsed laser with adjustable wavelengths.

Without solving at least one of the above-mentioned problems, the present application proposes a multi-wavelength photoacoustic imaging drive system, which realizes the combination of pulse and continuous modulation modes (two modes) through the principle of the method as shown in FIG. In the implementation example, the shortest pulse width is 40ns (nanoseconds), the maximum driving current is 13A, and the maximum modulation frequency is 3MHz, which are suitable for both time-domain and frequency-domain photoacoustic imaging. At the same time, combined with continuous laser diodes of multiple wavelengths, a low-cost multi-wavelength photoacoustic imaging system with laser diodes as the light source is realized.

In this embodiment, the formed pulsed laser 210 is a fixed-wavelength pulsed laser, for example, the pulsed laser is fixed at a wavelength of 450 nm, and the duration is 200 ns. Because it is a pulsed laser with a non-tunable wavelength, the price of the pulsed laser 210 used in the present application is greatly reduced compared to the pulsed laser with a tunable wavelength in the prior art.

In this embodiment, a schematic circuit diagram of the dual-mode laser driver 211 can be seen in FIG. 3 , which includes an operational amplifier U1 , a transistor Q1 , a second laser diode LD, and a transient voltage suppressor TVS.

The operational amplifier U1 includes: a first signal input terminal for inputting a trigger signal, a second signal input terminal coupled with a resistor R2, and a signal output terminal coupled with an adjustable resistor R1 between the transistor Q1 and the transistor Q1.

The transient voltage suppressor TVS is used to protect the laser diode LD (laser diode 212 described in FIG. 2 ) from damage from forward transient high voltage and reverse bias voltage.

It should be noted that the dual-mode laser 210 is based on the principle of a constant current source circuit, and due to the feedback loop, the current of the laser diode LD depends on the input voltage under continuous current control. Operational amplifier U1 is a high-speed operational amplifier, which, together with transistor Q1, enables fast switching. As in one or more realizable embodiments, the wavelength of the laser diode LD is 450 nm and the continuous current is 3A.

The transient voltage suppressor TVS is used to protect the laser diode LD from damage from forward transient high voltage and reverse bias voltage.

In one or more achievable embodiments, the model of the operational amplifier U1 is preferably EL2045C, the model of the transistor Q1 is preferably IRF7469, the model of the laser diode LD is preferably NDB7A75, and the adjustable resistor R1 The resistance value of R2 is preferably 1K, and the resistance value of the resistor R2 is preferably 0.5Ω.

In this embodiment, the pulsed laser 210 has a single wavelength, and the wavelengths of the continuous lasers 220 are different.

Preferably, the wavelengths of the CW lasers 220 in the present application can be respectively 450nm, 520nm, 638nm, 650nm, 808nm and 1064nm, and their maximum adjustable powers are respectively 1W, 0.7W, 1W, 1W, 0.4W, 2W and 3W.

In one or more achievable embodiments, the multi-wavelength photoacoustic imaging driving system 200 described in the present application can integrate and package a plurality of the CW lasers 220 of different wavelengths to drive different wavelengths, and through the metal base attached , for thermal diffusion, the size of the multi-wavelength photoacoustic imaging drive system 200 may be only about 23 mm×33 mm.

For example, in the pulse mode of the dual-mode laser driver 211, the input trigger signal adopts a logic (TTL, also called transistor-transistor logic level) voltage, VDD (operating voltage inside the device) and VCC (access circuit voltage) ) are equal to 20V. The results of pulse current generation are shown in FIG. 4 , which can illustrate different pulse widths and corresponding currents of the laser diode LD.

Specifically, the pulse width is calculated from the full width at half maximum (FWHM) of the pulse waveform. The minimum pulse width is 40ns and the maximum pulse width is 200ns. It can be seen that the peak current increases with increasing pulse width. This is because the current increase takes some time to settle, and when the input trigger duration is less than the current rise time, a longer trigger duration will result in a higher output current. The full width at half maximum of the laser is wider than the laser diode 212 current pulse width, and because the input resistance of the oscilloscope is 50Ω, the photodetector needs some time to discharge the charge. At the same time, the negative portion of the laser diode 212 current pulse is consumed by the transient voltage suppressor TVS, at which point the laser diode 212 is turned off. Therefore, the actual laser pulse width is equal to the laser diode 212 current pulse width.

For another example, in the continuous mode of the dual-mode laser driver 211 , the input trigger signal adopts an analog voltage of 0 to 1.5V, and both VDD and VCC are equal to 7V. The present application shows that all laser waveforms exhibit sinusoidal modulation following the input analog voltage through the current waveforms and corresponding optical waveforms of the CW laser 220 at modulation frequencies of 1 MHz, 2 MHz and 3 MHz (maximum frequency).

As shown in FIG. 5 , a schematic structural diagram of a multi-wavelength photoacoustic imaging experimental apparatus in an embodiment of the present application is shown. As shown in the figure, the multi-wavelength photoacoustic imaging experimental device 500 includes: the multi-wavelength photoacoustic imaging driving system 501 as shown in FIG. 2, a PC terminal 502, an ultrasonic transducer 503, a pulse generator receiver 504, and an oscilloscope 505, a stepping motor 506, and a function generator 507; wherein, the multi-wavelength photoacoustic imaging system 501 includes: a pulsed laser and a plurality of continuous lasers.

The PC terminal 502 is used to drive the pulsed laser light source and the continuous laser light source in a specific order.

In this embodiment, the specific sequence of driving the pulsed laser light source and the continuous laser light source is: pulsed laser light source-continuous laser light source-pulsed laser light source.

In this embodiment, the second pulse laser source in the specific sequence is triggered by the falling edge of the continuous laser in the multi-wavelength photoacoustic imaging driving system 501 to excite the second photoacoustic signal.

The ultrasonic transducer 503 is configured to receive the photoacoustic signal excited by the multi-wavelength photoacoustic imaging system 501 .

In some embodiments, the ultrasonic transducer 503 is placed in a water tank to detect the photoacoustic signal fed back by the received sample.

The pulse generator receiver 504 is used to further amplify the photoacoustic signal.

The oscilloscope 505 is used to collect and amplify the photoacoustic signal and transmit it to the PC terminal 502 for the PC terminal 502 to control the stepping motor 506 to move the laser source.

As shown in FIG. 6 , it is a schematic diagram showing a scene of a multi-wavelength photoacoustic imaging experimental apparatus in an embodiment of the present application. For example, the PC terminal 502 controls the function generator 507 to drive the laser source in a specific sequence (pulse-CW-pulse), and the second pulsed laser is triggered by the falling edge of the CW laser to excite the second photoacoustic signal, without unnecessary thermal diffusion. The repetition rate is 20Hz. By using a focusing lens (100 mm focal length), the pulsed laser spot was focused to 200 μm and the laser diode of the CW laser was focused to 1 mm diameter. The samples consisted of three silicone tubes filled with red, green and grey inks, respectively. The inner diameter of each tube is 0.8 mm. The generated photoacoustic signal is received by an ultrasonic transducer 503 (eg model I10C8F20, Doppler Inc.) having a center frequency of 10 MHz and a diameter of 10 mm, which will be further processed by a pulser receiver 504 (eg model 5072PR, Olympus Inc.) Amplify 45dB. An oscilloscope 505 (eg, model DPO5204B, Tektronix Inc.) collects the amplified photoacoustic signal and transmits it to the PC terminal 502 . The PC terminal 502 controls the stepper motor 506 to move the laser spot and the sensor to complete the raster scan.

In this application, the following example experiments are carried out by using the multi-wavelength photoacoustic imaging experimental device to illustrate the feasibility of the multi-wavelength photoacoustic imaging method, driving system and experimental device described in this application in detail.

First, a photoacoustic microscope (PAM) system for 2D imaging was constructed to conduct pulse modulation and continuous modulation photoacoustic imaging experiments. Please refer to the schematic diagram of the scene shown in FIG. 7 . Raster scanning is achieved by a linear translation stage controlled by a PC terminal (personal computer) to adjust the position of the water tank in the x-y plane. The imaging area is about 20mm×20mm, and the scanning step size is 0.4mm. A function generator (eg, model AFG1062, Tektronix Inc.) is controlled by the PC terminal to trigger the multi-wavelength photoacoustic imaging drive system. For time-domain photoacoustic imaging, the function generator outputs pulse signals with different durations, and different laser pulse widths (40 ns, 100 ns and 200 ns, respectively) are excited at a repetition rate of 1 KHz. For frequency-domain photoacoustic imaging, the chirp frequency was swept from 1 MHz to 3 MHz with a duration of 100 μs and a repetition rate of 100 Hz. The laser was weakly focused to a spot size of about 500 μm by a condenser lens (100 mm focal length). The sample phantom consisted of three silicon tubes filled with ink of different inner diameters (1 mm, 2 mm and 3 mm), with an effective length of approximately 10 mm. The resulting photoacoustic signal was received by an immersion focused ultrasound transducer (eg, model I10C8F20, Doppler Inc.) with a diameter of 10 mm, a center frequency of 10 MHz, and a fractional bandwidth of 80%. A pulser receiver (eg model 5072PR, Olympus) is used to amplify the PA signal with a gain of 45dB. Using an oscilloscope (eg, model DPO5204B, Tektronix Inc.), the signals in the time domain and frequency domain imaging were acquired by averaging 256 times and transmitted to the PC side.

To further verify the ability of the multi-wavelength photoacoustic imaging drive system for in vivo photoacoustic imaging, the ear of a 10-week-old mouse was also used as the imaging object. The imaging setup is shown in Figure 8. The laser spot was further focused to about 200 μm with a scan step size of 100 μm. For time-domain imaging, the pulse width was set to 200 ns. The frequency domain imaging modulation frequency is 1-3 MHz and the duration is 100 μs. The imaging area is approximately 5mm x 5mm. Because the mouse is fixed under the water tank, it is inconvenient to move the water tank. Therefore, for in vivo experiments, the laser was moved point by point under the control of a linear translation stage. The generated photoacoustic signal is coupled to the ultrasonic transducer through medical ultrasonic couplant, plastic wrap and water. Other system setups for in vivo imaging were the same as those for the silicon tube phantom experiments described above.

9A-9C show time-domain photoacoustic (PA) sensing with different laser pulse widths, respectively. Among them, photoacoustic signals with amplitudes of 8 mV, 25 mV and 34 mV were induced by pulsed laser widths of 40 ns, 100 ns and 200 ns, respectively.

As expected, increasing the pulse width from 40ns to 200ns resulted in an increase in the amplitude of the photoacoustic (PA) signal due to the increased energy absorbed by the sample. Therefore, the image contrast is also enhanced accordingly. However, the increase in amplitude is not linearly related to the pulse width, because the photoacoustic conversion efficiency will decrease when the phantom is irradiated with a laser with a longer pulse width. Using an optical power meter, the laser pulse energy of these three different pulse widths, 0.3 μJ, 1.8 μJ, and 3 μJ, can be measured and calculated. The corresponding laser energy densities are 0.04 mJ/cm ² , 0.24 mJ/cm ² and 0.4 mJ/cm ² , which are well within the ANSI maximum allowable exposure (20 mJ/cm ² ) for a 450 nm laser. In this case, the corresponding average optical powers emitted from the laser diodes are 0.3 mW, 1.8 mW and 3 mW, respectively.

The time-domain imaging results corresponding to the pulse widths of Figures 9A-9C are shown in Figure 10. From the amplitudes of the photoacoustic signal waveforms in Figure 10, it can be known that the photoacoustic (PA) conversion efficiencies of the three laser pulse widths are respectively are 1.67×104, 1.38×104 and 1.13×104(V/J), which means that the PA conversion efficiency decreases as the pulse width increases.

For frequency-domain photoacoustic sensing and imaging, Figures 11A-11B show the raw noise and photoacoustic signals before applying matched filters. It can be seen that the noise is larger than that of time-domain photoacoustic imaging. This is because the EMI noise generated by the 100 μs trigger signal couples into the transducer. Furthermore, the chirp duration (100 μs) is longer than the propagation time of the photoacoustic signal reaching the transducer (~10 μs), which makes the photoacoustic signal mix with noise. Since this noise has a similar spectrum to the photoacoustic signal, we subtract the noise from the photoacoustic signal before applying the matched filter to avoid artifacts. 11C-11D are the signal processing results after applying the matched filter. It can be seen that the noisy signal is still as noisy as before, but the matched-filtered photoacoustic signal shows strong peaks and the signal-to-noise ratio (SNR) is significantly improved. Figure 11E is the frequency domain photoacoustic imaging result of three silicon tubes.

To calculate the signal-to-noise ratio (SNR) of the photoacoustic image, regions containing only background noise in the image were selected to obtain the average noise magnitude. Compared with the SNRs of 9.30dB, 16.30dB and 16.92dB in the time-domain imaging results corresponding to the pulse widths in Figs. 9A-9C, the SNR in Fig. 10 is 24.16dB, which verifies the SNR. Photoacoustic imaging in the frequency domain will be better than in the time domain, with less average data. The laser fluence used for frequency domain imaging was 15 mJ/cm ² , which was also within the ANSI maximum allowable exposure (110 mJ/cm ² ) when the duration exceeded 10 μs. The corresponding average optical power emitted from the laser diode is 0.12W. Regarding the conversion efficiency of frequency-domain PA imaging, it can be calculated as: 3.88×103V/J. It is worth noting that, due to the need for more pulse energy, the conversion efficiency of frequency-domain PA is much lower than that of time-domain photoacoustic imaging (1.13×104V /J minimum) conversion efficiency. However, by applying a matched filter, the signal-to-noise ratio of the photoacoustic signal can be greatly enhanced. This is an interesting trade-off in frequency-domain photoacoustic imaging: sacrificing conversion efficiency for a higher signal-to-noise ratio.

The time-domain photoacoustic imaging results of the mouse ear using the multi-wavelength photoacoustic imaging experimental device including the multi-wavelength photoacoustic imaging drive system are shown in (b) of Figure 12, where the blood vessels of the mouse ear are clearly visible. As expected, the photoacoustic imaging in the frequency domain ((c) in Fig. 12) is clearer than the PA image in the time domain. Due to the reduction of the laser spot area, the laser energy density becomes 2.5 mJ/cm ² in pulsed photoacoustic imaging and 93.75 mJ/cm ² in frequency domain photoacoustic imaging, which are all within the maximum allowable exposure range of ANSI . It can be concluded that the imaging results match well with the real mouse ears shown in Fig. 12, with satisfactory image signal-to-noise ratios: 15.12dB ((b) in Fig. 12) and 22.54dB (Fig. 12), respectively in (c)).

There are two factors we should consider before ex vivo imaging experiments, namely the choice of CW laser wavelength and the heating duration Δt. They both affect imaging contrast.

Choice of CW laser wavelengths. We selected three wavelengths from the CW laser module based on the absorption spectrum of the sample. By using a spectrophotometer (such as model UV-8000, METASH Inc.) to obtain the light absorption spectrum shown in Figure 13, three wavelengths can be determined to be 520nm, 638nm and 808nm, because using these three wavelengths can convert the three colors The ink is clearly identified.

The maximum allowable exposure (MPE) of the laser should be considered before determining the duration of heating. Figure 14A is a graph of MPE for skin exposure to a laser beam based on selected wavelengths as a function of exposure duration representing the maximum allowable exposure. Heating energies (50, 100, 200, 300 and 400 mJ/cm ² ) were determined from several heating durations and the corresponding MPE summarized in the small table shown in Figure 14A to demonstrate the nonlinear effect of these heating durations. The variation of the photoacoustic signal along these heating durations and heating energy is shown in Figure 14B. The photoacoustic signal was generated by red ink and amplified by 45dB, then averaged 200 times. It can be seen that the slope of the curve for the 1ms heating duration is larger than any other curve, which means that the amplitude of the photoacoustic signal will increase more efficiently because the heat will not diffuse excessively during the 1ms heating duration. Therefore, the heating duration is selected to be 1 ms, and the heating energy is determined to be 50 mJ/cm ² to ensure the safety of practical application.

To demonstrate the selectivity of the samples to different wavelengths of laser light, the samples consisting of only the red ink were heated by CW lasers at 520, 638, and 808 nm, respectively. As shown in FIG. 15A , it is shown that the amplitude of the photoacoustic signal varies with the red ink before and after continuous laser heating with different wavelengths. As can be seen, only the CW laser at 520 nm can induce a significant increase in the amplitude of the photoacoustic signal, which matches well with the results in Figure 14B. Meanwhile, to demonstrate that the photoacoustic signal varies with different color inks, a 520nm CW laser was used to heat three ink tubes filled with red, green and gray inks, respectively. It can be seen from Figure 15B that the photoacoustic signal increases significantly after heating the red ink, which also matches well with the results in Figure 14B, where Figure 15B shows the amplitude of the acousto-optic signal before and after heating with a 520nm continuous laser Variations of three different color inks.

According to the above preliminary experiments, it can be concluded that the proposed multi-wavelength imaging system has the capability of multi-wavelength photoacoustic imaging. Next, we use 2D mechanical scanning. The imaging area is 10mm x 2mm. The photoacoustic signal was averaged 200 times and amplified by 45dB. The imaging results are shown in Figure 16. It is shown as the result of photoacoustic 2D imaging of three ink tubes filled with red, green and grey inks. The heating wavelengths in (a), (b) and (c) are 520 nm, 638 nm and 808 nm, respectively, BH: before heating; AH: after heating; DI: differential image. As shown in Fig. 16, the PA signal induced by the gray ink for the 450 nm pulsed laser is weaker than the photoacoustic signal induced by the red and green inks. However, the noise in the differential image in (c) of Figure 16 seems to be strong, because the gray ink cannot absorb the 808 nm laser light significantly, and then the signal amplitude before and after heating is not significantly different, which in turn makes it very noisy.

Still further, a multi-wavelength photoacoustic imaging system can be used to measure the ink content. Through this quantitative experiment, it is shown that this system has the potential to measure blood oxygen saturation.

First, the measurement system for the concentration ratio of red and green inks is introduced. A transparent rubber tube with an inner diameter of 0.8mm was filled with red and green inks of a specific concentration ratio and fixed in a water tank. Red-green inks were prepared and diluted in six concentration ratios (red ink 0%, 20%, 40%, 60%, 80% and 100%). According to the light absorption spectra of the red and green inks (as shown in Figure 13), the inks of these two colors have absorption peaks at 520 nm and 638 nm, respectively. Therefore, the continuous laser module of these two wavelengths is used to measure the red ink concentration, which can be expressed as:

in,

The photoacoustic measurement results are shown in Figures 17A and 17B. The 520nm and 638nm curves shown in Figure 17A show that with increasing red ink concentration, the 520nm curve increases and the 638nm curve decreases nonlinearly, implying that the measurements are reasonable. The red ink density was calculated and shown in Figure 17B, which exhibits a non-linear distribution along the preset red ink density. Therefore, it is necessary to calibrate the photoacoustic measurements. By fitting the measurements using a second-order polynomial, it can be seen from the 520 nm curve in Figure 17B that the R-squared is greater than 0.9. After calibration, the value in the red curve is the final concentration value, where the square point represents the measurement result and the curve represents the calibration result.

To sum up, a multi-wavelength photoacoustic imaging method, driving system and experimental device provided by this application use a single-wavelength pulsed laser source to excite a photoacoustic signal; use one or more continuous laser sources of different wavelengths for heating The imaging target can enhance the excited photoacoustic signal to different degrees, so as to realize multi-wavelength photoacoustic imaging.

The present application effectively overcomes various shortcomings in the prior art and has high industrial application value.

The above-mentioned embodiments merely illustrate the principles and effects of the present application, but are not intended to limit the present invention. Anyone skilled in the art can make modifications or changes to the above embodiments without departing from the spirit and scope of the present application. Therefore, all equivalent modifications or changes made by those skilled in the art without departing from the spirit and technical idea disclosed in the present invention should still be covered by the claims of the present application.

Claims (9)

1. a multi-wavelength photoacoustic imaging method, is characterized in that, described method comprises: A single wavelength pulsed laser source is used to excite the photoacoustic signal; One or more continuous laser sources with different wavelengths are used to heat the imaging target, so that the excited photoacoustic signals are enhanced to different degrees, so as to realize multi-wavelength photoacoustic imaging. 2. The method according to claim 1, wherein the photoacoustic signal is expressed as: p ₀ (λ _i )=Γ ₀ η _th μ _a (λ _i )F _pulse ,i=1,2,3...,,; where λ _i is the laser source wavelength, η _th is the conversion constant from optical absorption to heat, μ _a (λ _i ) is the optical absorption coefficient at wavelength λ _i , F _pulse is the pulsed optical flux assumed to be constant, Γ ₀ is the Grunesen parameter related to the local temperature. 3. The method according to claim 2, wherein the enhanced photoacoustic signal is expressed as:

Among them, the nonlinear effect term in the formula represents the enhanced part of the Gruneisen parameter after heating; b is the coefficient of absorbed thermal energy from heating to the change of the Gruneisen parameter, and τ _th is the thermal diffusivity of the sample , F _CW is the luminous flux of the CW laser source, and Δt is the duration of the CW laser source irradiation. 4. A multi-wavelength photoacoustic imaging drive system, wherein the drive system comprises: a pulsed laser and a plurality of continuous lasers; Wherein, the pulsed laser includes a dual-mode laser driver and a laser diode, the pulsed laser is used to provide a pulsed laser source to excite the photoacoustic signal; the continuous laser is used to provide a plurality of continuous laser sources of different wavelengths to heat the imaging target . 5. The driving system according to claim 4, wherein the dual-mode laser driver comprises: an operational amplifier, a transistor, and a transient voltage suppressor; The operational amplifier includes: a first signal input end for inputting a trigger signal, a second signal input end coupled with a resistor, and a signal output end coupled with the transistor with an adjustable resistance; The transient voltage suppressor is used to protect the laser diode from damage from forward transient high voltage and reverse bias voltage. 6 . The driving system according to claim 4 , wherein the pulsed laser has a single wavelength, and the wavelengths of the continuous lasers are different. 7 . 7. A multi-wavelength photoacoustic imaging experimental device, characterized in that, the experimental device comprises: the multi-wavelength photoacoustic imaging drive system described in any one of claims 4 to 7, a PC terminal, an ultrasonic transducer energy generators, pulse generator receivers, oscilloscopes, stepper motors, and function generators; The PC terminal is used to drive the pulsed laser light source and the continuous laser light source in a specific order; the ultrasonic transducer for receiving the photoacoustic signal excited by the multi-wavelength photoacoustic imaging system; the pulse generator receiver for further amplifying the photoacoustic signal; The oscilloscope is used to collect and amplify the photoacoustic signal and transmit it to the PC, so that the PC can control the stepping motor to move the laser source. 8 . The experimental device according to claim 7 , wherein the specific sequence of driving the pulsed laser source and the continuous laser source is: pulsed laser source-continuous laser source-pulsed laser source. 9 . 9. The experimental device according to claim 8, wherein the second pulse laser source in the specific sequence is triggered by the falling edge of the continuous laser diode driver in the multi-wavelength photoacoustic imaging driving system, to excite the second photoacoustic signal.

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