Microvascular evaluation device based on photoacoustic measurement of laser diode

Abstract

The invention discloses a microvessel evaluation device based on laser diode photoacoustic measurement, the device comprises a laser diode, a laser diode pulse driver, an ultrasonic sensor, a pulse receiver and an oscilloscope, the laser diode pulse driver is used for controlling the laser diode to emit laser to irradiate a target microvessel; the ultrasonic sensor is used for receiving a photoacoustic signal in a target micro blood vessel and transmitting the signal to the pulse receiver; the pulse receiver is used for filtering the photoacoustic signal and then transmitting the photoacoustic signal to the oscilloscope; the filtered photoacoustic signals are observed through an oscilloscope, and the microvascular occlusion degree is evaluated. The device provided by the invention is low in cost, realizes evaluation of the occlusion degree of the microvessel based on photoacoustic measurement of the laser diode, can assist in diagnosing the condition of microarteriosclerosis, and provides reference for the design of arteriosclerosis diagnosis equipment in the future.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and more particularly to a microvascular evaluation device based on laser diode photoacoustic measurement. Background Art

[0002] In recent years, the incidence of arteriosclerotic diseases has gradually increased. If this disease progresses to the late stage, it may cause serious problems such as myocardial infarction or cerebral infarction. At present, although there have been many studies on the diagnosis of relatively thick blood vessels, the sclerosis of microvessels cannot be ignored. If the microarteries in the brain and kidneys become sclerotic, blood flow will be blocked, which is called microarteriosclerosis. It mainly appears in the arteries with a diameter of 0.5-1 mm distributed in parts such as the basal ganglia area of the brain and the kidneys. Generally, when plaques form in the blood vessels, the inner diameter of the blood vessels becomes narrower and blood flow deteriorates, which may lead to serious diseases such as acute myocardial infarction or cerebral infarction.

[0003] Currently, existing non-invasive observation methods can only cover relatively thick blood vessels (such as blood vessels with a diameter of 2-6 mm or more), and it is difficult to infer the sclerosis of sub-millimeter microvessels. Moreover, the cost of the observation equipment is also high. Microarteriosclerosis is usually a systemic symptom. Observing the state of microarteries such as fingertips is of great significance for the diagnosis of microarteriosclerosis. Therefore, there is an urgent need to develop relevant observation devices for microvascular evaluation. Summary of the Invention

[0004] In view of this, the present invention provides a microvascular evaluation device based on laser diode photoacoustic measurement that solves at least the above partial technical problems. The device has a simple structure and low cost, and realizes the evaluation of the occlusion degree of microvessels based on laser diode photoacoustic measurement, which can assist in the diagnosis of microarteriosclerosis and provide a reference for the design of future arteriosclerosis diagnosis devices.

[0005] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0006] In a first aspect, the present invention provides a microvascular evaluation device based on laser diode photoacoustic measurement for assisting in the diagnosis of the occlusion degree of microvessels, including: a laser diode, a laser diode pulse driver, an ultrasonic sensor, a pulse receiver, and an oscilloscope, wherein:

[0007] The laser diode is connected to the laser diode pulse driver; the ultrasonic sensor, the pulse receiver, and the oscilloscope are connected in sequence;

[0008] The laser diode pulse driver is used to control the laser diode to emit laser light to irradiate the target microvessel; the ultrasonic sensor is used to receive the photoacoustic signal in the target microvessel and transmit the signal to the pulse receiver; the pulse receiver is used to filter the photoacoustic signal and then transmit it to the oscilloscope, and the filtered photoacoustic signal is observed through the oscilloscope to evaluate the degree of microvessel occlusion.

[0009] In an alternative embodiment, the device further includes: a collimating lens, which is disposed at the front end of the laser diode and is used to collimate and focus the laser light emitted by the laser diode.

[0010] In an alternative embodiment, the device further includes: a low-noise amplifier, which is respectively connected to the ultrasonic sensor and the pulse receiver and is used to amplify the photoacoustic signal and transmit the amplified signal to the pulse receiver.

[0011] In an alternative embodiment, the ultrasonic sensor employs a planar transducer with a central frequency of 2 MHz and a diameter of 14 mm.

[0012] In an alternative embodiment, the cut-off frequencies of the high-pass and low-pass filters of the pulse receiver are respectively set to 1 kHz and 20 MHz.

[0013] In an alternative embodiment, the device further includes a computing device, which is equipped with an evaluation module. The evaluation module evaluates the degree of microvessel occlusion through the frequency characteristics and resonance intensity of the photoacoustic signal; the calculation formula for the resonance intensity is:

[0014]

[0015] where β represents the resonance intensity; f0 represents the peak frequency in the frequency characteristics; f1 and f2 are two frequency points when the signal amplitude is the peak frequency f0 times.

[0016] In an alternative embodiment, the evaluation module utilizes a trained fully connected neural network model, with the frequency characteristics and resonance intensity of the photoacoustic signal as the neuron inputs and the degree of microvessel occlusion as the output, to achieve intelligent evaluation of the degree of microvessel occlusion.

[0017] Compared with the prior art, the present invention has at least the following beneficial technical effects:

[0018] The present invention provides a microvessel evaluation device based on laser diode photoacoustic measurement. The device has a simple structure and low cost, and can evaluate the degree of microvessel occlusion based on laser diode photoacoustic measurement, which can assist in diagnosing the condition of microvascular arteriosclerosis and provide a reference for the design of future arteriosclerosis diagnosis devices.

[0019] Other features and advantages of the present invention will be set forth in the following description, and in part will be obvious from the description, or may be learned by practice of the present invention. The objectives and other advantages of the present invention may be realized and attained by the structure particularly pointed out in the written description and drawings.

[0020] The technical solutions of the present invention will be further described in detail below with reference to the drawings and embodiments. Description of the Drawings

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present application. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0022] The drawings are used to provide a further understanding of the present invention, and constitute a part of the description. Together with the embodiments of the present invention, they are used to explain the present invention, and do not constitute a limitation to the present invention.

[0023] Figure 1 Schematic structural diagram of a microvascular evaluation device based on laser diode photoacoustic measurement provided for an embodiment of the present invention.

[0024] Figure 2 Schematic diagram of the experimental setup and sample preparation principle provided for an embodiment of the present invention.

[0025] Figure 3 Schematic diagram of five different levels (cross-sectional area) of pipe blockage modes provided for an embodiment of the present invention.

[0026] Figure 4 Schematic diagram of photoacoustic time waveforms at different occlusion rates provided for an embodiment of the present invention.

[0027] Figure 5 Schematic diagram of the relationship between the occlusion rate and the photoacoustic signal amplitude provided for an embodiment of the present invention.

[0028] Figure 6 Schematic diagram of the frequency characteristics of photoacoustic signals at different occlusion degrees provided for an embodiment of the present invention.

[0029] Figure 7 Schematic diagram of a simulation model provided for an embodiment of the present invention.

[0030] Figure 8 Schematic diagram of the frequency response (plaque from 0% to 100%) provided for an embodiment of the present invention.

[0031] Figure 9 Schematic diagram for comparison of resonance frequencies at different plaque ratios provided by an embodiment of the present invention.

[0032] Figure 10 Schematic diagram for definition of β provided by an embodiment of the present invention.

[0033] Figure 11 Schematic diagram for comparison of β values between silicone tubes with and without tallow provided by an embodiment of the present invention. Detailed implementation manners

[0034] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. Generally, the components of the embodiments of the present invention described and illustrated in the accompanying drawings here can be arranged and designed in various different configurations.

[0035] The exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. Although the exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided so that the present disclosure can be more thoroughly understood and the scope of the present disclosure can be fully conveyed to those skilled in the art.

[0036] See Figure 1 As shown, an embodiment of the present invention provides a microvascular evaluation device based on laser diode photoacoustic measurement. The device is used to assist in diagnosing the degree of microvascular occlusion and includes: a laser diode, a laser diode pulse driver, an ultrasonic sensor, a pulse receiver, and an oscilloscope, where:

[0037] The laser diode is connected to the laser diode pulse driver; the ultrasonic sensor, the pulse receiver, and the oscilloscope are connected in sequence;

[0038] The laser diode pulse driver is used to control the laser diode to emit laser light to irradiate the target microvessel; the ultrasonic sensor is used to receive the photoacoustic signal in the target microvessel and transmit the signal to the pulse receiver; the pulse receiver is used to filter the photoacoustic signal and then transmit it to the oscilloscope; the filtered photoacoustic signal is observed through the oscilloscope to evaluate the degree of microvascular occlusion.

[0039] In a preferred embodiment, the device further includes: a collimating lens, which is arranged at the front end of the laser diode and is used to collimate and focus the laser light emitted by the laser diode.

[0040] In a preferred embodiment, the device further comprises: a low-noise amplifier, which is respectively connected to the ultrasonic sensor and the pulse receiver, and is configured to amplify the photoacoustic signal and transmit the amplified signal to the pulse receiver.

[0041] In a preferred embodiment, the device further comprises a computing device, in which an evaluation module is installed. The evaluation module evaluates the degree of microvascular occlusion through the frequency characteristics and resonance intensity of the photoacoustic signal. Preferably, the evaluation module utilizes a trained fully-connected neural network model, with the frequency characteristics and resonance intensity of the photoacoustic signal as the neuron inputs and the degree of microvascular occlusion as the output, to achieve intelligent evaluation of the degree of microvascular occlusion, which helps to improve the efficiency and accuracy of the evaluation.

[0042] The following combines Figures 1 to 11 as shown, and details the principles and specific implementation manners involved in the present invention through the experimental process:

[0043] In order to diagnose microvessels with a diameter less than 1 mm, the present invention has developed a composition architecture of a diagnostic device using a laser diode. In the experiment, a laser diode with a power of about 20 mW was used, and a silicon tube partially filled with tallow was used to simulate the vascular occlusion situation. The experimental results of five vascular samples with different occlusion degrees were studied. The resonance peak and its sharpness reflect the degree of vascular occlusion. The results can provide a reference for the design of future arteriosclerosis diagnostic devices.

[0044] In this experiment, the device developed by the present invention uses a low-power semiconductor laser as the light source to measure the photoacoustic signal intensity of a glass capillary or silicone tube sample with an outer diameter of about 1 mm filled with the target liquid, so as to evaluate the performance of the contrast agent for photoacoustic measurement. The principle of photoacoustic measurement is that when a nanosecond-level excitation light pulse is irradiated on the sample absorber, the absorber absorbs the energy of the excitation light and converts it into heat energy through the heat diffusion equation. Due to this heat conversion, the absorber will generate a temperature distribution different from that of the surrounding area and undergo thermal expansion. The thermal expansion will generate a force to restore the object to its original state, and finally generate a photoacoustic signal through the thermoelastic process and the wave equation. This study shows that the acoustic resonance in the capillary affects the photoacoustic signal, and it is found that the acoustic mode in the capillary and the elastic characteristics of the capillary have a significant impact on the frequency response and directivity of the photoacoustic signal. In addition, a basic study on photoacoustic measurement was carried out using a phantom model embedded with a silicone tube simulating a biological blood vessel and a mixture of ink and oil imitating arteriosclerotic blood. The research results show that the oil concentration can be inferred using the photoacoustic signal intensity.

[0045] High levels of low-density lipoprotein (LDL, commonly known as "bad cholesterol") over a long period can cause LDL to accumulate on the inner walls of blood vessels, forming plaques. As the plaques gradually grow, their surface may suddenly rupture, and platelets will aggregate at the rupture site to form a large mass called a thrombus, further narrowing the blood vessel. In the present invention, in order to simulate an occluded blood vessel, a commercially available beef tallow was used to partially fill a silicone tube, and five types of blood vessel samples with different occlusion degrees were fabricated to experimentally study the relationship between the frequency characteristics of photoacoustic signals and the amount of plaque in the blood vessel. The specific experimental content is as follows:

[0046] Experimental preparation:

[0047] Materials such as a silicone tube were embedded in a soft mold (artificial skin gel EXSEAL, H00600J) with a size of approximately 30 mm square, and the test liquid was sealed. According to Figure 2 the method, the excitation light was irradiated from above, and the photoacoustic signal was received from the side. A semiconductor laser with a wavelength of 520 nm was used as the excitation light source, and a planar transducer (JAPAN PROBE, 2K10I) with a center frequency of 2 MHz and a diameter of 14 mm was used for the detection of photoacoustic signals. The electrical signal of the ultrasonic transducer was amplified by a 40 dB low-noise amplifier (SA-240F5, NF) and then connected to a pulse receiver (5900PR, Panametrics). The cut-off frequencies of the high-pass and low-pass filters of the pulse receiver were set to 1 kHz and 20 MHz respectively, and the attenuation was set to 54 dB. The received signal was observed using a digital oscilloscope with sufficient bandwidth. The detailed composition of the device hardware structure is shown in Figure 1 the figure.

[0048] To simulate a blood vessel narrowed by plaque, commercially available beef tallow was partially filled in the silicone tube, and five types of samples were fabricated as shown in Figure 3 the figure: non-occluded tube, 54% occlusion, 78% occlusion, 91% occlusion, and completely occluded tube. The method for fabricating the occluded blood vessel model is as follows: First, a thin metal wire was inserted into the silicone tube to create a partially occluded state, and then liquid beef tallow heated to a liquid state was injected with a syringe. After cooling and solidifying, the metal wire was removed, and red ink as a blood substitute was filled in the gap. Since the excitation light wavelength is 520 nm, red ink is considered to be the main photoacoustic absorber. To avoid difficulty in filling beef tallow due to too small an inner diameter, a silicone tube with an inner diameter of 1 mm and an outer diameter of 2 mm was used in this experiment.

[0049] Effect of beef tallow filling on photoacoustic signals:

[0050] Figure 4The measured time waveform of the photoacoustic signal is shown. Since the 520 nm laser light used in the experiment is less absorbed in beef tallow, no obvious signal was detected in the completely occluded silicone tube. In addition, the signal in the partially occluded tube showed more obvious oscillations and resonances compared to the photoacoustic signal when only ink was present, but with a smaller amplitude. This may be due to the lower acoustic impedance of the silicone tube wall compared to beef tallow, which increases the reflection coefficient of the signal in the ink.

[0051] As Figure 5 shown, as the occlusion rate increases, the amplitude of the photoacoustic signal gradually decreases. This decrease in amplitude is considered to be because, with the same laser light focusing degree, the higher the occlusion rate, the less red ink is excited.

[0052] Frequency response at different occlusion rates:

[0053] Furthermore, as Figure 6 shown, which summarizes the frequency characteristics of the photoacoustic signal at different occlusion levels, and these results were obtained by performing a fast Fourier transform (FFT) on the time waveform. After introducing beef tallow, the silicone tube forms a multi-layer structure, and two resonance peaks appear in all occluded tubes. In addition, as the occlusion degree increases, the cross-sectional area of the liquid part decreases, resulting in an increase in the resonance frequency and an increase in the peak frequency.

[0054] To explore the experimental results, a finite element method (FEM) simulation was performed using the Figure 7 shown two-dimensional blood vessel cross-sectional model. The outer diameter of the pipe was set to 1 mm and the inner diameter to 0.5 mm, and a sound source was configured at the central position within the inner diameter range. Although the light incident from above would actually be gradually absorbed and scattered and attenuated in reality, it was simplified to a sound source with a constant intensity along the radial direction in the calculation. In addition, to facilitate the calculation and evaluation of the frequency characteristics, the sound source was set as a continuous sine wave.

[0055] Simulated plaques were axially symmetrically set within the inner diameter range, and the acoustic properties of the plaques were close to those of low-density lipoprotein (LDL, bad cholesterol). The plaque ratios were set to 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, and a total of 11 modes of simulation were performed.

[0056] Furthermore, as Figure 8 shown, the frequency characteristics obtained from the simulation at different plaque ratios are shown. As the beef tallow increases, the frequency peak splits into two, and the frequency difference between the two peaks gradually increases. In addition, the frequency of the high-value peak was compared with the occlusion degree and plotted together with the experimental results as Figure 9 shown. It can be confirmed that the stenosis caused by the plaque leads to a monotonic increase in the peak frequency.

[0057] Next, as Figure 10As shown, the resonance intensity β of the signal is defined by the following formula:

[0058]

[0059] where f0 represents the peak frequency in the frequency characteristic, and f1 and f2 are two frequency points when the signal amplitude is times the peak frequency f0. The higher the β value, the sharper the resonance of the frequency characteristic; the lower the β value, the flatter the resonance.

[0060] In the present invention, the β values of silicone tubes with and without beef tallow were compared, and the results are as Figure 11 shown. The β value of the silicone tube containing beef tallow is about 3 times that of the silicone tube without beef tallow, indicating that the occluded tube exhibits stronger signal resonance. This shows that as plaque accumulates and blood vessels narrow, the frequency characteristic of the photoacoustic signal is sharper compared to the healthy state.

[0061] From the description of the above embodiments, those skilled in the art can learn that: in response to the need for the evaluation of microvessels such as fingertips, the present invention provides a microvessel evaluation device based on laser diode photoacoustic measurement. The device has a simple structure and low cost; the basic characteristics of a platform for quantitatively evaluating vascular occlusion degree are explored by using a low-power pulsed semiconductor laser and an MHz bandwidth ultrasonic transducer. Five samples with different occlusion degrees are made by partially filling commercially available beef tallow in a silicone tube to simulate occluded blood vessels. Experimental studies on the photoacoustic characteristics of each sample show that: as the occlusion degree of beef tallow in the silicone tube increases, the amplitude of the photoacoustic signal decreases, the peak frequency of the frequency characteristic increases, and the resonance intensity increases. The evaluation of the degree of microvascular occlusion based on laser diode photoacoustic measurement can assist in the diagnosis of microvascular arteriosclerosis. Based on the structure of this device, it can provide a reference for the design of future arteriosclerosis diagnosis devices and develop a miniaturized photoacoustic device capable of observing actual fingertip blood vessels.

[0062] It should be noted that the word "comprising" does not exclude the existence of modules, components or steps not listed in the claims. The word "a" or "an" preceding a component does not exclude the existence of a plurality of such components. The present invention can be implemented by means of hardware including several different components and by means of a suitably programmed computer.

[0063] In this specification, the various embodiments are described in a progressive manner. Each embodiment focuses on the differences from other embodiments. The same or similar parts among the various embodiments can be referred to each other.

[0064] The foregoing description of the disclosed embodiments enables those skilled in the art to practice or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A microvascular assessment device based on laser diode photoacoustic measurement, characterized in that: The device is used for assisting diagnosis of microvascular occlusion, and comprises: a laser diode, a laser diode pulse driver, an ultrasonic sensor, a pulse receiver and an oscilloscope, wherein: The laser diode is connected to the laser diode pulse driver; the ultrasonic sensor, pulse receiver and oscilloscope are connected in sequence; The laser diode pulse driver is used to control the laser diode to emit laser to irradiate the target microvessel; the ultrasonic sensor is used to receive the photoacoustic signal in the target microvessel and transmit the signal to the pulse receiver; the pulse receiver is used to filter the photoacoustic signal and transmit it to the oscilloscope, and the filtered photoacoustic signal is observed by the oscilloscope to evaluate the degree of microvascular occlusion.

2. The microvascular assessment device based on laser diode photoacoustic measurement according to claim 1, characterized in that: The device also includes a collimating lens, which is arranged at the front end of the laser diode and is used for collimating and focusing the laser emitted by the laser diode.

3. The microvascular assessment device based on laser diode photoacoustic measurement according to claim 1, characterized in that: The device also includes: a low noise amplifier, which is connected to the ultrasonic sensor and the pulse receiver respectively, and is used to amplify the photoacoustic signal and transmit the amplified signal to the pulse receiver.

4. The microvascular assessment device based on laser diode photoacoustic measurement according to claim 1, characterized in that: The ultrasonic sensor adopts a planar transducer with a center frequency of 2 MHz and a diameter of 14 mm.

5. The microvascular assessment device based on laser diode photoacoustic measurement according to claim 1, characterized in that: The high-pass and low-pass filter cutoff frequencies of the pulse receiver are set to 1kHz and 20MHz respectively.

6. The microvascular assessment device based on laser diode photoacoustic measurement according to claim 1, characterized in that: The device also includes a computing device, which is equipped with an evaluation module. The evaluation module evaluates the degree of microvascular occlusion through the frequency characteristics and resonance intensity of the photoacoustic signal; the calculation formula of the resonance intensity is: Where β represents the resonance intensity; f0 represents the peak frequency in the frequency characteristic; f1 and f2 are the signal amplitudes at the peak frequency f0. Two frequency points when the value is doubled.

7. The microvascular assessment device based on laser diode photoacoustic measurement according to claim 6, characterized in that: The evaluation module utilizes a trained fully connected neural network model, takes the frequency characteristics and resonance intensity of the photoacoustic signal as neuron input, and the degree of microvascular occlusion as output, to achieve intelligent evaluation of the degree of microvascular occlusion.

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