CN117017280A - Wearable flexible near-infrared photoacoustic/ultrasonic dual-mode imaging system and method - Google Patents
Wearable flexible near-infrared photoacoustic/ultrasonic dual-mode imaging system and method Download PDFInfo
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- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
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- A61B5/0095—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy by applying light and detecting acoustic waves, i.e. photoacoustic measurements
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Abstract
The application discloses a wearable flexible near-infrared photoacoustic/ultrasonic bimodal imaging system and method, comprising the following steps: a pen-type laser for generating a laser light source; a wearable flexible near infrared transparent ultrasound transducer for transmitting ultrasound signals or for receiving and transmitting photoacoustic signals generated when a pen-type laser irradiates a blood vessel. The photoacoustic/ultrasonic bimodal imaging system has a compact overall structure, and can be used for conveniently, real-time and continuously and dynamically detecting important physiological parameters of the chest central blood vessel.
Description
Technical Field
The application relates to the technical field of wearable flexible near-infrared transparent ultrasonic transducers, in particular to a system and a method for forming a dual-mode image based on wearable flexible near-infrared photoacoustic/ultrasonic.
Background
Oxygen is a gas necessary to maintain the normal metabolism and vital activities of the body. The blood carries oxygen to circulate in the cardiovascular system, thus realizing the transportation of substances required by the metabolism of cells in the whole body. Blood oxygen saturation and blood flow dynamics are important physiological parameters for evaluating metabolism and functions of human tissues, and can be used as key predictors for disease diagnosis and progress.
Current blood oxygen saturation detection techniques mainly include invasive blood gas analysis and non-invasive pulse oximetry. However, blood gas analysis is highly specialized in operation, may cause local infection, and cannot provide real-time continuous detection information. Pulse oximeters utilizing pure optical imaging principles, while providing safe, effective and continuous dynamic detection, lack of spatial resolution and limited imaging depth. The detection of blood flow dynamics in clinic is mainly based on ultrasonic imaging technology, and vascular ultrasound can accurately reflect the vascular anatomy structure and key blood flow dynamics information of artery and vein through technologies such as color Doppler blood flow imaging, contrast agent, three-dimensional blood vessel imaging construction and the like.
Photoacoustic imaging is a novel imaging technique that combines the advantages of high contrast optical imaging and deep penetration acoustic imaging, and is capable of providing not only visualization of the anatomy of the vasculature, but also functional information and kinetic signals in the form of blood oxygenation, blood flow, and temperature. And the ultrasonic transducer array based on photoacoustic imaging detection can be combined with ultrasonic echo signals for integrating photoacoustic modes and mature ultrasonic technology so as to promote bimodal imaging of image post-processing and obtain a result with more reference value. With the development of clinical transformation research of a handheld photoacoustic/ultrasonic bimodal imaging system, at present, an attempt of bimodal imaging is firstly carried out in thyroid cancer, breast cancer, blood oxygen saturation, rheumatoid arthritis and other diseases. However, currently known bimodal imaging systems are still relatively bulky and cannot provide real-time, continuous dynamic images.
In addition, peripheral circulation such as fingertips, wrists and arms responds slower to respiratory cardiac arrest and acute ischemia and hypoxia events than the central blood vessel site based on blood redistribution and oxygen storage and their distal positions in the heart, so a method based on thoracic central blood vessel to detect signals such as blood oxygen saturation, blood flow dynamics and the like may be a promising technology. Although this approach suffers from problems such as respiratory artefacts and poor sternal perfusion, and chest-based detection devices have not been strictly validated, clinical study evaluations have shown that chest-based detection of heart rate, respiratory rate and blood oxygen saturation is feasible. Therefore, a novel wearable flexible near-infrared transparent photoacoustic/ultrasonic bimodal imaging system based on the chest and capable of detecting the blood oxygen saturation of the central blood vessel and the hemodynamic signals is explored, so that the requirements of convenient, rapid and real-time continuous dynamic detection are met, and more possibilities are provided for individualized diagnosis and treatment.
Disclosure of Invention
The application aims to provide a wearable flexible near-infrared photoacoustic/ultrasonic bimodal imaging system and method, aiming at solving the technical problems in the background technology.
In order to achieve the above purpose, the present application adopts the following technical scheme:
a wearable flexible near infrared photoacoustic/ultrasound based bimodal imaging system comprising:
a pen-type laser for generating a laser light source;
a wearable flexible near infrared transparent ultrasound transducer for transmitting ultrasound signals or for receiving and transmitting photoacoustic signals generated when a pen-type laser irradiates a blood vessel.
In some embodiments, the pen laser includes:
the shell is internally provided with a mounting cavity;
a high efficiency laser diode array, the Gao Xiaoji array of light diodes being located within the mounting cavity;
the laser driver is positioned in the mounting cavity and is arranged at the top of the high-efficiency laser diode array;
the cylindrical lens is positioned in the mounting cavity and is arranged at the bottom of the high-efficiency laser diode array;
the diffraction optical element is positioned in the mounting cavity, and the laser driver, the high-efficiency laser diode array, the cylindrical lens and the diffraction optical element are connected through the substrate;
one end of the trigger is connected with the laser driver, and the other end of the trigger is connected with the shell;
and the round glass is arranged at the head part of the shell.
In some embodiments, a Polydimethylsiloxane (PDMS) flexible substrate, a plurality of micro-rigid CMUT elements, a serpentine silver nanowire electrode, and an electrode connected to the outside, the plurality of micro-rigid CMUT elements being arranged in parallel, the micro-rigid CMUT elements, the serpentine silver nanowire electrode, and the electrode connected to the outside being co-packaged in the PDMS flexible substrate based on the silver nanowire electrode being connected to each other to form a serpentine interconnect line.
In some embodiments, the miniature rigid CMUT element consists of an Indium Tin Oxide (ITO) top electrode, a vibrating membrane, a capacitor plate structure with a vacuum cavity, an ITO bottom electrode, and a substrate; the top electrode is fixed on the upper surface of the vibrating membrane, and the capacitor plate structure with the vacuum cavity is attached to the lower surface of the vibrating membrane; the ITO bottom electrode is attached to the lower part of the capacitor plate structure with the vacuum cavity, and the substrate is attached to the lower part of the ITO bottom electrode; the vibrating membrane is a silicon nitride vibrating membrane, and the substrate is a silicon crystal substrate.
In some embodiments, the capacitor plate structure with the vacuum cavity comprises a plurality of insulators BCB, wherein two insulators BCB distributed on the side part and an insulator BCB distributed on the bottom part form a sealed vacuum cavity together with a vibrating membrane; the capacitor plate structure with the vacuum cavity is composed of a plurality of insulators BCB, a vibrating diaphragm and the vacuum cavity.
The embodiment also provides a wearable flexible near-infrared photoacoustic/ultrasonic bimodal imaging method, which is realized based on the system and comprises the following steps:
irradiating the chest central blood vessel by using a pen-type laser to emit near infrared laser beams to generate photoacoustic signals;
adjusting parameters of the ultrasonic scanner to switch to a photoacoustic imaging mode;
a wearable flexible near infrared transparent ultrasonic transducer attached to the chest receives the photoacoustic signal;
constructing a light absorption distribution diagram of the hemoglobin by utilizing an image reconstruction algorithm, and quantifying the blood oxygen saturation according to the absorption coefficient of the hemoglobin;
switching the ultrasound scanner to an ultrasound imaging mode;
transmitting pulse ultrasonic waves through a wearable flexible near infrared transparent ultrasonic transducer to detect a chest central blood vessel, and simultaneously receiving echo signals of a reflector;
b-type gray scale mode images of the chest central blood vessels are displayed by using an image reconstruction algorithm; calculating blood pressure of blood flow in blood vessels based on B-type gray scale mode images of chest central blood vessels; the information and spatial distribution of the flowing blood flow velocity is detected by the doppler effect.
In some embodiments, the near infrared laser beam has a wavelength of 900-1100 nm.
In some embodiments, the quantifying the blood oxygen saturation according to the absorption coefficient of hemoglobin comprises:
at wavelength lambda 1 And lambda (lambda) 2 The absorption coefficient mu is smaller than the preset condition λ Can be calculated by formulas (1) and (2):
wherein C is Hb And C HbO2 Respectively the deoxyhemoglobin and oxyhemoglobin contents;and->Respectively represent deoxyhemoglobin and oxyhemoglobin at wavelength lambda 1 And lambda (lambda) 2 An extinction coefficient of (a);
blood oxygen saturation SaO 2 Can be calculated by the formulas (3), (4) and (5):
in some embodiments, the computing blood pressure of the blood flow in the blood vessel from the B-mode gray scale pattern image of the thoracic center blood vessel comprises:
the blood pressure waveform (pr (t)) can be calculated from the blood vessel diameter waveform by the formula (6):
pr d is the brachial artery diastolic pressure measured by a cuff sphygmomanometer; ar (ar) d Is the cross section of arterial diastole;
alpha is the rigidity coefficient of the blood vessel and can be calculated by the formula (7):
Pr s is the brachial artery systolic pressure measured by a commercial cuff sphygmomanometer; ar (ar) s Is the cross section of the systolic phase of the artery;
ar (t) can be calculated by equation (8):
d (t) is a vessel diameter waveform measured by a wearable flexible near infrared transparent ultrasound transducer.
In some embodiments, detecting the flow velocity information and spatial distribution of flowing blood by doppler effect includes:
detecting flowing blood information through Doppler effect, adopting multiple acoustic beams to perform rapid sampling, performing phase detection, autocorrelation processing and color coding on the obtained Doppler information, marking blood flow directions by different colors, displaying the speed of color brightness, and superposing the color brightness on a B-type gray scale ultrasonic image to obtain the spatial distribution and flow velocity information of blood flow in blood vessels;
the blood flow velocity (v) of the arterial vessel can be calculated by the formula (9) using the doppler principle:
c is the speed of sound, i.e. the propagation speed of ultrasound in soft tissue; f (f) 0 Is the transmit frequency; f (f) d Is the doppler shift, i.e., the difference between the received frequency and the transmitted frequency; θ is the Doppler angle, the angle between the ultrasound beam and the direction of blood flow motion.
Compared with the prior art, the application has the following beneficial effects:
(1) In view of the fact that near infrared wavelength emitted by the pen-shaped laser can penetrate to a depth of several centimeters, limitation of penetration depth of optical imaging is broken through, and real-time dynamic detection of blood oxygen saturation of a chest central blood vessel can be achieved.
(2) The wearable flexible near infrared transparent ultrasonic transducer is thin, light and compact in structure, can be closely attached to the chest skin, is suitable for any shape of a contact interface, and can be self-aligned to a target interface so as to meet clinical requirements of continuous detection.
(3) The integration of the light source and the ultrasonic transducer not only avoids the management of the light source, but also greatly reduces the whole size, facilitates the scanning and obviously reduces the scanning time.
(4) The photoacoustic/ultrasonic bimodal imaging system has a compact overall structure, and can be used for conveniently, real-time and continuously and dynamically detecting important physiological parameters of the chest central blood vessel.
Drawings
Fig. 1 is a schematic structural diagram of a pen-type laser according to an embodiment.
Fig. 2 is a schematic structural diagram of a wearable flexible near infrared transparent ultrasonic transducer in an embodiment.
Fig. 3 is a schematic structural diagram of a rigid CMUT in an embodiment.
Fig. 4 is a schematic diagram of the working principle of the photoacoustic/ultrasonic bimodal imaging system in the embodiment.
Fig. 5 is a schematic structural view of a photoacoustic/ultrasound bimodal imaging system for detecting a thoracic center vessel.
Detailed Description
In order to make the objects, technical solutions and advantages of the present application more apparent, the technical solutions in the preferred embodiments of the present application will be described in more detail with reference to the accompanying drawings in the preferred embodiments of the present application. In the drawings, the same or similar reference numerals refer to the same or similar components or components having the same or similar functions throughout. The described embodiments are some, but not all, embodiments of the application. The embodiments described below by referring to the drawings are illustrative and intended to explain the present application and should not be construed as limiting the application. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Embodiments of the present application will be described in detail below with reference to the accompanying drawings.
In the description of the present application, it should be noted that, unless explicitly stated and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be fixedly connected, or indirectly connected through intermediaries, for example, or may be in communication with each other between two elements or in an interaction relationship between the two elements. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art according to the specific circumstances.
In the description of the present application, it should be understood that the terms "upper," "lower," "front," "rear," "vertical," "horizontal," "top," "bottom," "inner," "outer," and the like indicate or are based on the orientation or positional relationship of the drawings, merely to facilitate description of the present application and simplify the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be configured and operated in a specific orientation, and thus should not be construed as limiting the present application.
Furthermore, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or display that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed or inherent to such process, method, article, or display.
A detailed description of a wearable flexible near-infrared based photoacoustic/ultrasound bimodal imaging system in accordance with embodiments of the present application will be provided below in conjunction with fig. 1-5. It is noted that the following examples are only for explaining the present application and are not to be construed as limiting the present application.
Example 1:
as shown in fig. 1-5, a wearable flexible near-infrared photoacoustic/ultrasound based bimodal imaging system comprising: a pen-type laser 1 for generating a laser light source, a wearable flexible near infrared transparent ultrasonic transducer 2; the wearable flexible near infrared transparent ultrasound transducer is used for transmitting ultrasound signals or for receiving and transmitting photoacoustic signals generated when the pen-type laser irradiates the blood vessel 3.
The pen-shaped laser realizes the free control of the emission of laser through an external trigger, and when the pen-shaped laser is integrated with an ultrasonic transducer and applied to a photoacoustic imaging system, the pen-shaped laser ensures the synchronous proceeding of near infrared light irradiation and photoacoustic signal reception, thereby realizing the continuous, real-time and dynamic detection of deep tissues.
The pen-type laser can activate the laser driver 12 by controlling the trigger 11 connected to the outside, thereby driving the high-efficiency diode array 13 to emit laser beams, so that the process of irradiating deep tissues with near infrared laser can be freely controlled. When a pen-type laser is integrated with an ultrasonic transducer and applied to a photoacoustic imaging system, this is important for synchronization of laser irradiation and photoacoustic signal reception.
The three-dimensional view of the pen-type laser shows a cylindrical structure, the length of the cylinder is 12cm, and the diameter of the bottom surface is 3cm. The body part located in the center of the pen-shaped laser is a high-efficiency laser diode array, and the laser driver and the cylindrical lens are located at the top and bottom of the array respectively. The laser driver, the high-efficiency laser diode array, the cylindrical lens 14, and the diffractive optical element 15 are connected by a substrate. The top of laser driver is connected with the one end of trigger, and the other end of trigger is connected with the afterbody of cylinder shell to realize the free control laser emission through outside shift knob, in order to satisfy the basic condition of optoacoustic imaging. The circular glass 17 forms the head of a cylindrical housing, and the housing 16 is made of aluminum and has a cooling function to limit the increase in heat.
By pressing a trigger connected to the tail of the pen-shaped laser, a laser driver connected to the other end of the trigger can be started, thereby driving the high-efficiency laser diode array connected by the substrate to emit a near infrared laser beam. The quality of the emitted laser beam is poor and the divergence is very pronounced, so that an optical system is required to achieve collimation and reshaping of the laser beam to minimize energy loss and to ensure that the region of interest of the deep tissue is illuminated with the desired laser beam profile. The emitted laser beam is first collimated by a cylindrical lens placed in front of the high efficiency laser diode array to minimize beam divergence and achieve beam shaping. The collimated laser beam is reshaped by a diffractive optical element, homogenized and irradiated in rectangular form through a circular glass at the bottom of the pen-shaped laser to the region of interest.
The portable pen-type laser provided by the application has a compact structure, realizes miniaturization of an illumination system, and is easy to integrate in a photoacoustic imaging system. The near infrared laser beam emitted by the pen-shaped laser has larger penetration depth, which is beneficial to imaging deep tissues.
The wearable flexible near infrared transparent ultrasonic transducer provided by the application allows near infrared laser beams to penetrate for photoacoustic/ultrasonic imaging so as to realize wider clinical application scenes.
The wearable flexible near infrared transparent ultrasonic transducer is formed by mutually connecting a series of micro CMUT rigid elements through a snake-shaped silver nano line and encapsulating the flexible MEMS rigid elements in flexible Polydimethylsiloxane (PDMS). The device has compact structure, allows near infrared light to penetrate, can be comfortably attached to the surface of a target tissue, can transmit and/or receive ultrasonic signals, obtains continuous, real-time and high-quality detection images, and can be applied to ultrasonic imaging and photoacoustic imaging systems.
The wearable flexible near infrared transparent ultrasonic transducer comprises: the PDMS flexible substrate 21, a plurality of miniature rigid CMUT elements 22, a serpentine silver nanowire electrode 23 and an electrode 24 connected with the outside, wherein the miniature rigid CMUT elements are arranged in parallel, the serpentine interconnection line is formed by mutually connecting the silver nanowire electrodes, and the rigid CMUT elements, the serpentine silver nanowire electrode and the electrode connected with the outside are packaged in the PDMS flexible substrate together.
The miniature rigid CMUT element consists of an ITO top electrode 25, a vibrating membrane 26, a capacitor plate structure with a vacuum cavity, an ITO bottom electrode and a substrate; the top electrode is fixed on the upper surface of the vibrating membrane, and the capacitor plate structure with the vacuum cavity is attached to the lower surface of the vibrating membrane; the ITO bottom electrode is attached to the lower part of the capacitor plate structure with the vacuum cavity, and the substrate is attached to the lower part of the ITO bottom electrode 29; the diaphragm is a silicon nitride diaphragm and the substrate is a silicon crystal substrate 30.
The capacitor plate structure with the vacuum cavity comprises a plurality of insulators BCB, wherein the insulators BCB distributed on the side parts, the insulators BCB distributed on the bottom parts and the vibrating membrane form a sealed vacuum cavity 27; the capacitor plate structure with the vacuum cavity is composed of a plurality of insulators BCB28, a vibrating membrane and the vacuum cavity.
When the CMUT is in operation, a dc bias voltage is typically applied to sink the diaphragm into the vacuum chamber, such that the stress of the diaphragm can increase the sensitivity of the transducer. When transmitting or transmitting ultrasonic waves, an alternating current signal is superimposed with an applied direct current bias voltage. The dc voltage brings the top electrode and the bottom electrode closer together, and the ac voltage drives the diaphragm to generate an ultrasonic signal, the driving frequency of which is the transmission frequency of the ultrasonic wave. When receiving ultrasonic signals, only direct current voltage is applied to keep a fixed potential difference, and the incident sound wave can modulate the height of a vacuum cavity gap according to the frequency of the wave so as to change the capacitance of the vibrating membrane, thereby generating output current. The output current is converted into a voltage signal and enhanced by a transimpedance amplifier to effect reception of the signal.
Manufacturing a serpentine silver nanowire electrode: the silver nanowires were mixed with silver flake ink, and then the mixed silver nanowire/silver composite ink was screen printed on a PDMS-based flexible substrate using a screen printer at room temperature. In this process, a custom screen with serpentine pattern open areas is used as a printing template and silver nanowires/silver composite ink is added to the custom screen. Thus, when the scraper scrapes across the surface of the screen, the silver nanowire/silver composite ink can be left on the PDMS of the flexible substrate through the open area in the screen, thereby forming a serpentine pattern. All the interconnection electrode wires connected with the ultrasonic transducer and the electrode wires connected with the outside are constructed by the screen printing technology.
Manufacturing of CMUT rigid element: CMUT is prepared by an adhesive wafer bonding process, and styrene-acrylate-butylene (BCB) is a photosensitive polymer, which is used as an adhesive and a sidewall layer of the CMUT. The CMUT closed vacuum chamber structure is more advantageous and has better performance in controlling the size, shape and membrane material uniformity of the chamber.
First, two wafers, a silicon wafer I containing silicon nitride and a silicon substrate wafer II, are prepared. And (3) placing the wafer in a mixed solution of hydrogen peroxide and concentrated sulfuric acid for oxidation dissolution, and cleaning metal impurities.
A silicon nitride layer is deposited on a silicon nitride wafer one using a low pressure chemical vapor deposition process to build a low stress diaphragm. And removing the silicon nitride on the back surface of the vibrating membrane under the condition that the photoresist protects the front surface of the vibrating membrane by using photoetching and reactive ion etching processes, and stripping the photoresist on the front surface to form the silicon nitride on the vibrating membrane of the CMUT element.
In order to increase the optical transmittance of the silicon crystal substrate, three key manufacturing steps are required: (1) And grinding and thinning the second silicon substrate wafer to realize thinning of the thickness of the silicon substrate and reduction of light absorption. (2) The chemical mechanical polishing process is used to realize the finish of the mirror surface and reduce the scattering of infrared light in the illumination process to the greatest extent. (3) An anti-reflection coating is added to the surface of the silicon substrate to achieve higher optical transmittance.
An ITO bottom electrode was formed by sputtering a 250nm layer of transparent conductive material Indium Tin Oxide (ITO) on a second silicon substrate wafer. And then cleaning in a mixed solution of ammonium hydroxide, hydrogen peroxide and deionized water to remove any possible organic pollutants, wherein the ammonia and the hydrogen peroxide can clean particles attached to the surface of the silicon wafer and improve the cleanliness of the particles, and the cleanliness of the particles directly influences the bonding effect of the next step.
To ensure proper adhesion of BCB to the ITO bottom electrode, a thin layer of AP3000 adhesive (dow chemical) was first spin coated on a second silicon substrate wafer at 3000rpm for 30 seconds and then soft baked at 150 ℃ for 60 seconds. This step also needs to be performed on the silicon nitride wafer one to improve adhesion in the adhesive bonding step later in the process. Subsequently, BCB was spin coated on silicon substrate wafer two at 6500rpm for 45 seconds and soft baked at 60 ℃ for 90 seconds. The BCB layer is exposed to uv light and then baked at 50 c for 60 seconds. Subsequently, the cavity was defined by spin drying for 2 minutes after 2 minutes of rinsing with DS2100 developer. The thickness of the BCB layer determines the gap distance of the CMUT cell.
And bonding the first silicon nitride wafer and the second silicon substrate wafer together by using a wafer bonding machine through an adhesive. The wafers are first separated by a spacer to ensure a vacuum-tight gap. After loading the wafers, the chamber was pumped down to 0.5mTorr and the gasket removed allowing the two wafers to contact each other while forming a vacuum tight chamber. Then, a compression pressure of 0.5MPa was applied to the wafer for 1 hour, and the wafer was cooled and taken out of the chamber. The process of removing the wafer silicon handle is accelerated by a combination of dry etching and wet etching.
A 200nm transparent conductive material ITO layer was sputtered on a silicon nitride diaphragm as a top electrode, and then the top ITO layer was patterned using a positive photoresist and wet etching to define a top electrode of the CMUT cell. To reduce the resistivity of the top electrode and maintain the transparency of the device, patterning is performed in the form of thin strips by lift-off techniques. Subsequently, the wafer is diced in predefined horizontal and vertical directions using a dicing tool, diced into chip islands with individual CMUT elements, rapidly spin coated with a PDMS flexible layer on the back of the wafer and cured. And finally, packaging the serpentine silver nanowire interconnection electrode and the CMUT array in the PDMS flexible substrate at the same time to form the flexible near infrared transparent CMUT array.
Some key design factors including diameter, material type and vacuum gap height are considered in manufacturing CMUTs, which may affect the performance of CMUTs. CMUT is modeled as a second order system to obtain important parameters such as resonant frequency and pull-in voltage.
The resonant frequency (ω0) is a key parameter that determines the resolution of an image.
t represents the thickness of the diaphragm, a is the radius of the diaphragm, E represents the Young's modulus of the diaphragm material, v is the Poisson's ratio of the diaphragm, ρ m Is the density of the medium and ρ is the density of the film.
Another key parameter is the pull-in voltage (V pull in ). The pull-in voltage is the point at which the electrostatic and mechanical forces are equal, which results in the top electrode being stuck to the substrate. Therefore, it is very important to operate the CMUT below the pull-in voltage.
g eff Represents the effective gap height and has the calculation formula ofg 0 Is the original gap height, t m Is the thickness of the film, t i Is the thickness of the insulator, epsilon r Is the relative dielectric constant, epsilon, of the insulator and film materials 0 Is the dielectric constant of free space, k isSpring constant, a, is electrode area.
The wearable flexible near infrared transparent ultrasonic transducer has a light and thin and soft structure, can adapt to any shape of a contact interface, and can be self-aligned to a target interface so as to meet clinical requirements of continuous detection. The wearable flexible near infrared transparent ultrasonic transducer allows near infrared laser beams to penetrate, and the integration of a light source and the ultrasonic transducer can be effectively realized.
The embodiment also provides a wearable flexible near-infrared photoacoustic/ultrasonic bimodal imaging method, which is realized based on the system and comprises the following steps:
irradiating the chest central blood vessel by using a pen-type laser to emit near infrared laser beams to generate photoacoustic signals;
adjusting parameters of the ultrasonic scanner to switch to a photoacoustic imaging mode;
a wearable flexible near infrared transparent ultrasonic transducer attached to the chest receives the photoacoustic signal;
constructing a light absorption distribution diagram of the hemoglobin by utilizing an image reconstruction algorithm, and quantifying the blood oxygen saturation according to the absorption coefficient of the hemoglobin;
switching the ultrasound scanner to an ultrasound imaging mode;
transmitting pulse ultrasonic waves through a wearable flexible near infrared transparent ultrasonic transducer to detect a chest central blood vessel, and simultaneously receiving echo signals of a reflector;
b-type gray scale mode images of the chest central blood vessels are displayed by using an image reconstruction algorithm; calculating blood pressure of blood flow in blood vessels based on B-type gray scale mode images of chest central blood vessels; the information and spatial distribution of the flowing blood flow velocity is detected by the doppler effect.
The pen-shaped laser is driven by a customized laser driver, the driver emits a near infrared laser beam after being triggered by an external trigger (namely a switch button), at this time, the commercial ultrasonic scanner 4 is synchronously adjusted, the transmission function of ultrasonic waves is prevented, the switching to a photoacoustic imaging mode state is allowed, and the process of laser pulse irradiation and echo signal receiving can be synchronously performed. After the laser beam irradiates the chest central blood vessel, the local tissue causes the thermoelastic expansion effect, generates a photoacoustic signal and continuously propagates outwards to the skin surface, the photoacoustic signal is received by a wearable flexible near infrared transparent ultrasonic transducer attached to the chest, a light absorption distribution diagram of hemoglobin is constructed by utilizing an image reconstruction algorithm, and the oxygen saturation of blood is quantified according to the absorption coefficient of the hemoglobin.
In the near infrared spectrum range adopted by the system, the change of carbohemoglobin and methemoglobin is not considered, so the absorption of light mainly reflects the deoxidized hemoglobin (Hb) and the oxygenated hemoglobin (HbO) 2 ) Is a total concentration of (2).
In some embodiments, the near infrared laser beam has a wavelength of 900-1100 nm. The imaging system uses near infrared wavelengths as the appropriate spectral range. The depth of the biological tissue penetrable by the near infrared laser is as long as a few centimeters, and the hemoglobin has strong absorption advantage compared with other endogenous chromophores in the near infrared wavelength range. The difference in absorption rate between deoxyhemoglobin and oxyhemoglobin is most pronounced in the 900-1100 nm wavelength range. Furthermore, based on the low absorptivity of silicon to near infrared wavelengths, near infrared light can pass through the CMUT array without strong attenuation, so that the generated photoacoustic signal is successfully received by the wearable flexible near infrared transparent ultrasound transducer.
The quantifying the oxygen saturation of blood based on the absorption coefficient of hemoglobin comprises:
at wavelength lambda 1 And lambda (lambda) 2 The absorption coefficient mu is smaller than the preset condition λ Can be calculated by formulas (1) and (2):
wherein C is Hb And C HbO2 Respectively the deoxyhemoglobin and oxyhemoglobin contents;and->Respectively represent deoxyhemoglobin and oxyhemoglobin at wavelength lambda 1 And lambda (lambda) 2 An extinction coefficient of (a);
knowing that the intensity of the photoacoustic signal is proportional to the absorption coefficient of the tissue, the post-equation blood oxygen saturation SaO is simplified 2 Can be calculated by the formulas (3), (4) and (5):
subsequently, the commercial ultrasonic scanner is restarted to be in an ultrasonic imaging mode, and the chest central blood vessel is detected through the wearable flexible near infrared transparent ultrasonic transducer so as to realize ultrasonic imaging detection. The wearable flexible near infrared transparent ultrasonic transducer is attached to the corresponding skin surface of the chest central blood vessel, the CMUT array continuously transmits short pulse ultrasonic waves at a certain fixed frequency, and all array elements of the phased array element array participate in the transmission of each acoustic wave beam. The CMUT array transmits pulsed ultrasonic waves along the transmission path of each acoustic beam line, and then receives and processes echo signals of each reflector on the acoustic beam path one by one from shallow and deep. And displaying a B-type gray scale mode image of the chest central blood vessel by using an image reconstruction algorithm.
The arterial vessel under test is known to meet the following conditions: the blood pressure waveform (pr (t)) is calculated from the vessel diameter waveform by equation (6) with the feature of rotational symmetry, having certain elasticity and very small viscoelasticity:
the blood pressure waveform (pr (t)) can be calculated from the blood vessel diameter waveform by the formula (6):
pr d is the brachial artery diastolic pressure measured by a cuff sphygmomanometer; ar (ar) d Is the cross section of arterial diastole;
alpha is the rigidity coefficient of the blood vessel and can be calculated by the formula (7):
Pr s is the brachial artery systolic pressure measured by a commercial cuff sphygmomanometer; ar (ar) s Is the cross section of the systolic phase of the artery;
ar (t) can be calculated by equation (8):
d (t) is a vessel diameter waveform measured by a wearable flexible near infrared transparent ultrasound transducer.
In some embodiments, detecting the flow velocity information and spatial distribution of flowing blood by doppler effect includes:
detecting flowing blood information through Doppler effect, adopting multiple acoustic beams to perform rapid sampling, performing phase detection, autocorrelation processing and color coding on the obtained Doppler information, marking blood flow directions by different colors, displaying the speed of color brightness, and superposing the color brightness on a B-type gray scale ultrasonic image to obtain the spatial distribution and flow velocity information of blood flow in blood vessels;
the blood flow velocity (v) of the arterial vessel can be calculated by the formula (9) using the doppler principle:
c is the speed of sound, i.e. the propagation speed of ultrasound in soft tissue; f (f) 0 Is the transmit frequency; f (f) d Is the doppler shift, i.e., the difference between the received frequency and the transmitted frequency; θ is the Doppler angle, the angle between the ultrasound beam and the direction of blood flow motion.
Therefore, the photoacoustic/ultrasonic bimodal imaging system can realize real-time, continuous and dynamic detection of blood oxygen saturation and hemodynamic information of the chest central blood vessel.
The foregoing description of the preferred embodiments of the application is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the application.
Claims (10)
1. A wearable flexible near infrared photoacoustic/ultrasound bimodal imaging system comprising:
a pen-type laser for generating a laser light source;
a wearable flexible near infrared transparent ultrasound transducer for transmitting ultrasound signals or for receiving and transmitting photoacoustic signals generated when a pen-type laser irradiates a blood vessel.
2. The wearable flexible near infrared photoacoustic/ultrasound bimodal imaging system of claim 1 wherein the pen laser comprises:
the shell is internally provided with a mounting cavity;
a high efficiency laser diode array, the Gao Xiaoji array of light diodes being located within the mounting cavity;
the laser driver is positioned in the mounting cavity and is arranged at the top of the high-efficiency laser diode array;
the cylindrical lens is positioned in the mounting cavity and is arranged at the bottom of the high-efficiency laser diode array;
the diffraction optical element is positioned in the mounting cavity, and the laser driver, the high-efficiency laser diode array, the cylindrical lens and the diffraction optical element are connected through the substrate;
one end of the trigger is connected with the laser driver, and the other end of the trigger is connected with the shell;
and the round glass is arranged at the head part of the shell.
3. The wearable flexible near infrared photoacoustic/ultrasound bimodal imaging system of claim 2 wherein the wearable flexible near infrared transparent ultrasound transducer comprises: the MEMS flexible substrate comprises a PDMS flexible substrate, a plurality of micro-rigid CMUT elements, a serpentine silver nanowire electrode and an electrode connected with the outside, wherein the micro-rigid CMUT elements are arranged in parallel, the serpentine interconnection circuit is formed based on the interconnection of the silver nanowire electrodes, and the micro-rigid CMUT elements, the serpentine silver nanowire electrode and the electrode connected with the outside are packaged in the PDMS flexible substrate together.
4. The wearable flexible near infrared photoacoustic/ultrasound bimodal imaging system of claim 3 wherein the miniature rigid CMUT element consists of an ITO top electrode, a vibrating membrane, a capacitor plate structure with a vacuum cavity, an ITO bottom electrode and a substrate; the top electrode is fixed on the upper surface of the vibrating membrane, and the capacitor plate structure with the vacuum cavity is attached to the lower surface of the vibrating membrane; the ITO bottom electrode is attached to the lower part of the capacitor plate structure with the vacuum cavity, and the substrate is attached to the lower part of the ITO bottom electrode; the vibrating membrane is a silicon nitride vibrating membrane, and the substrate is a silicon crystal substrate.
5. The wearable flexible near infrared photoacoustic/ultrasound bimodal imaging system of claim 3 wherein the capacitor plate structure with vacuum cavity comprises several pieces of insulator BCB, wherein two pieces of insulator BCB distributed on the side and insulator BCB distributed on the bottom and vibrating membrane form a sealed vacuum cavity; the capacitor plate structure with the vacuum cavity is composed of a plurality of insulators BCB, a vibrating diaphragm and the vacuum cavity.
6. A wearable flexible near-infrared photoacoustic/ultrasound bimodal imaging method characterized in that it is realized based on the system according to any one of claims 1-5, comprising the following steps:
irradiating the chest central blood vessel by using a pen-type laser to emit near infrared laser beams to generate photoacoustic signals;
adjusting parameters of the ultrasonic scanner to switch to a photoacoustic imaging mode;
a wearable flexible near infrared transparent ultrasonic transducer attached to the chest receives the photoacoustic signal;
constructing a light absorption distribution diagram of the hemoglobin by utilizing an image reconstruction algorithm, and quantifying the blood oxygen saturation according to the absorption coefficient of the hemoglobin;
switching the ultrasound scanner to an ultrasound imaging mode;
transmitting pulse ultrasonic waves through a wearable flexible near infrared transparent ultrasonic transducer to detect a chest central blood vessel, and simultaneously receiving echo signals of a reflector;
b-type gray scale mode images of the chest central blood vessels are displayed by using an image reconstruction algorithm; calculating blood pressure of blood flow in blood vessels based on B-type gray scale mode images of chest central blood vessels; the information and spatial distribution of the flowing blood flow velocity is detected by the doppler effect.
7. The wearable flexible near infrared photoacoustic/ultrasound bimodal imaging method of claim 6 wherein the wavelength of the near infrared laser beam is 900 to 1100nm.
8. The wearable flexible near infrared photoacoustic/ultrasound bimodal imaging method of claim 6, wherein the quantifying the blood oxygen saturation according to the absorption coefficient of hemoglobin comprises:
at wavelength lambda 1 And lambda (lambda) 2 The absorption coefficient mu is smaller than the preset condition λ Can pass through the formula(1) And (2) calculating:
wherein C is Hb And C HbO2 Respectively the deoxyhemoglobin and oxyhemoglobin contents; epsilon λ1 Hb ，ε λ2 Hb And epsilon λ1 HbO2， ε λ2 HbO2 Respectively represent deoxyhemoglobin and oxyhemoglobin at wavelength lambda 1 And lambda (lambda) 2 An extinction coefficient of (a);
blood oxygen saturation SaO 2 Can be calculated by the formulas (3), (4) and (5):
9. the wearable flexible near infrared photoacoustic/ultrasound bimodal imaging method of claim 6 wherein the calculating the blood pressure of the blood flow within the blood vessel from the B-mode gray scale mode image of the thoracic center blood vessel comprises:
the blood pressure waveform (pr (t)) can be calculated from the blood vessel diameter waveform by the formula (6):
pr d is the brachial artery diastolic pressure measured by a cuff sphygmomanometer; ar (ar) d Is the cross section of arterial diastole;
alpha is the rigidity coefficient of the blood vessel and can be calculated by the formula (7):
Pr s is the brachial artery systolic pressure measured by a commercial cuff sphygmomanometer; ar (ar) s Is the cross section of the systolic phase of the artery;
ar (t) can be calculated by equation (8):
d (t) is a vessel diameter waveform measured by a wearable flexible near infrared transparent ultrasound transducer.
10. The wearable flexible near infrared photoacoustic/ultrasound bimodal imaging method of claim 6, wherein detecting the flowing blood flow velocity information and spatial distribution by doppler effect comprises:
detecting flowing blood information through Doppler effect, adopting multiple acoustic beams to perform rapid sampling, performing phase detection, autocorrelation processing and color coding on the obtained Doppler information, marking blood flow directions by different colors, displaying the speed of color brightness, and superposing the color brightness on a B-type gray scale ultrasonic image to obtain the spatial distribution and flow velocity information of blood flow in blood vessels;
the blood flow velocity (v) of the arterial vessel can be calculated by the formula (9) using the doppler principle:
c is the speed of sound, i.e. the propagation speed of ultrasound in soft tissue; f (f) 0 Is the transmit frequency; f (f) d Is the doppler shift, i.e., the difference between the received frequency and the transmitted frequency; θ is the Doppler angle, the angle between the ultrasound beam and the direction of blood flow motion.
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| CN118078221A (en) * | 2024-04-29 | 2024-05-28 | 华南师范大学 | Real-time feedback interactive free touch scanning three-dimensional photoacoustic imaging method and system |
| CN118078221B (en) * | 2024-04-29 | 2024-08-09 | 华南师范大学 | Real-time feedback interactive free touch scanning three-dimensional photoacoustic imaging method and system |
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