阅读说明：本技术 可穿戴式动物光声联合心电测量系统 (Wearable animal photoacoustic combined electrocardiogram measuring system ) 是由 李凯述 于 2019-08-28 设计创作，主要内容包括：本发明涉及一种可穿戴式动物光声联合心电测量系统,包括：光声测量系统,测量动物的光声信号；心电测量系统,测量动物的心电信号；信号处理系统,对光声测量系统测量得到的光声信号以及心电测量系统测量得到的心电信号进行处理；信号输出系统,输出经过处理的光声信号以及心电信号；光声探测器系统和心电测量系统均采用穿戴式。本发明的系统可以使动物在清醒且自由活动的状态下同时进行光声和心电测量的系统,提高操作的便利性、重复性,减小动物感染,同时可以进行长期的试验观察。(The invention relates to a wearable animal photoacoustic combined electrocardio-measuring system, which comprises: a photoacoustic measurement system that measures a photoacoustic signal of an animal; the electrocardio measuring system is used for measuring electrocardiosignals of animals; the signal processing system is used for processing the photoacoustic signal measured by the photoacoustic measurement system and the electrocardiosignal measured by the electrocardio measurement system; a signal output system for outputting the processed photoacoustic signal and the processed electrocardiographic signal; the photoacoustic detector system and the electrocardio measuring system are both wearable. The system can simultaneously perform photoacoustic and electrocardio measurement on the animals in a waking and freely moving state, improve the convenience and repeatability of operation, reduce animal infection and simultaneously perform long-term experimental observation.)

1. A wearable animal photoacoustic combined electrocardio-measurement system comprises:

a photoacoustic measurement system that measures a photoacoustic signal of an animal;

the electrocardio measuring system is used for measuring electrocardiosignals of animals;

the signal processing system is used for processing the photoacoustic signal measured by the photoacoustic measurement system and the electrocardiosignal measured by the electrocardio measurement system;

A signal output system for outputting the processed photoacoustic signal and the processed electrocardiographic signal;

The system is characterized in that the photoacoustic measurement system comprises a light source system and a photoacoustic detector system, the light source system adopts a pulse laser, the photoacoustic detector system adopts a wearable ultrasonic transducer array system, and the electrocardio measurement system adopts a wearable electrocardio measurement electrode for measurement;

the wearable ultrasonic transducer array system comprises a flexible substrate, an ultrasonic transducer array carried by the flexible substrate and adjustable belt parts extending from the flexible substrate to two sides, wherein the flexible substrate can be bent, the ultrasonic transducer array adopts a curved ultrasonic transducer array, and a photoacoustic detector system consisting of the flexible substrate and an ultrasonic transducer conforms to the curve of an animal part to be measured; the photoacoustic probe system is fixed to the animal body after the bands extending to both sides are combined, the bands may be integrally manufactured and have elasticity, or the bands may be combined at the combining portion, and the combining portion may be a hook and loop portion for length adjustment.

2. the system of claim 1, wherein the wearable electrocardiographic measurement system is an adjustable length flexible belt extending from the flexible substrate, the belt having a fixed loop at a distal end thereof for holding the electrocardiograph electrodes, the fixed loop comprising a variable length portion and a fixed length portion, the electrocardiograph electrodes being disposed at the fixed length portion; when the electrocardiogram electrode is used, after the limb part or the ear part of the tested animal passes through the fixing ring, the fixing ring is contracted due to the elasticity of the length-variable part, so that the electrocardiogram electrode is firmly contacted with the limb part or the ear part of the tested animal, and the electrocardiogram measurement is carried out.

3. the system as claimed in claim 1 or 2, wherein the pulsed laser is capable of emitting light of both red and infrared wavelengths, so that the photoacoustic measurement system is capable of measuring the blood oxygen saturation of the subject animal.

4. The system as claimed in claim 4, wherein the signal output system is a display for simultaneously displaying the photoacoustic image, the blood oxygen saturation image and the electrocardiogram of the subject animal.

5. the system as claimed in any one of claims 1, 2 or 4, wherein the photoacoustic detector system and the electrocardiograph measurement system are provided in the form of a pet dress, the photoacoustic detector system is provided in a main body part of the pet dress, the electrocardiograph measurement system is provided in limbs of the pet dress, the pet dress worn on the body part serves as a carrier of the ultrasonic transducer system, carries the ultrasonic transducer array, and the part worn on the limbs serves as a carrier of the electrocardiograph electrodes, and carries the electrocardiograph electrodes.

6. The system of claim 1 or 2, further comprising a liquid aerosolization device to aerosolize a medication for treatment of the disease, such that the medication is inhaled by the animal during free movement, thereby monitoring the cardiovascular status and the cardiac function status of the animal after the inhalation of the medication.

Technical Field

the invention relates to the field of medical imaging, in particular to an animal photoacoustic combined electrocardio-measuring system.

background

Photoacoustic imaging combines the advantages of both acoustic and optical imaging and has thus become one of the most rapidly developing biomedical imaging technologies in the last decade. Photoacoustic imaging is a novel composite imaging method that acquires the optical absorption characteristics of a sample by detecting acoustic signals generated by the photoacoustic effect and constructs a two-dimensional tomographic image or a three-dimensional stereoscopic image of the sample. Photoacoustic imaging can have higher contrast than ultrasonic imaging in terms of measuring density, elasticity parameters, and the like, and can also sensitively reflect the physiological structure of a living body and provide functional information of the living body. The photoacoustic imaging also has the advantages of large imaging depth and high deep tissue imaging resolution, the space resolution of the photoacoustic imaging can reach 1/200 of the imaging depth, and meanwhile, the photoacoustic imaging is safer to biological tissues. Due to the advantages of photoacoustic imaging, photoacoustic imaging can study cardiovascular diseases (angiogenesis/growth, myocarditis, thrombus, myocardial infarction, etc.) of a small animal living body, and at the same time, can output quantitative data of hemoglobin concentration and blood oxygen saturation, etc.

the existing photoacoustic imaging of animals such as mice is to place the mice below an imaging system with a large volume, and in order to ensure that the effect is not influenced by the movement of the mice during imaging, the mice are anesthetized by drugs and then fixed below an imaging probe, and are in a non-waking state after being anesthetized, so that the cardiovascular and the brain of the mice are influenced by the anesthetics, and the normal activities of the mice are not favorably observed; because the mouse is under anesthesia, it is not mobile and cannot perform other activity-related (e.g., footprint, bounce, etc.) detections than photoacoustic detection.

the electrocardio of the animal is monitored, for example, the electrocardio of the rat is monitored, because the electrocardio, the blood pressure and the vascular resistance of the rat are sensitive to the drug reaction, the electrocardio, the blood pressure and the vascular resistance of the rat are suitable for screening new drugs and researching cardiovascular pharmacology and the like, and the animal can be made into various tumor models and the like, and the electrocardio, the blood pressure and the vascular resistance of the rat are of great significance for the research of tumor and pharmacolog. The existing means for carrying out animal electrocardio monitoring generally comprises implanting an electrocardioelectrode or clamping the electrode on four limbs of an animal by adopting a clamp and the like, and generally carrying out the electrocardio monitoring after anesthetizing the animal. Implanted electrodes can cause trauma to the animal, causing infection in addition to pain to the animal; when the electrodes are clamped on four limbs, the movement of animals is limited, the animals do not like human bodies, when the human bodies adopt clamp-type electrocardio leads, the animals can be cooled and calm in modes of deep breathing and the like, the electrocardio is accurately measured, after the animals are implanted into the electrodes or clamped with the electrodes, tension, mania and the like can occur due to pain, and the measured electrocardio data are inaccurate.

There have been some studies in China to study a photoacoustic imaging system which keeps a mouse awake and is performed under a freely movable condition, such as an animal head-mounted photoacoustic imaging apparatus disclosed in CN104545814A, and although the mouse can be moved in a waking free state, an imaging probe is sutured to the head of the animal, and the suturing process thereof is traumatic to the mouse and causes infection, which is not humane; CN103976709A discloses a wearable array transducer probe that uses a bowl-shaped housing to arrange the transducers, but the bowl-shaped housing can only perform photoacoustic measurements of the head, not other tails. Moreover, these devices are not capable of performing electrocardiographic measurements and are limited in the need to understand the functional status of the heart of the animal. At present, no system is available for simultaneously carrying out photoacoustic imaging and electrocardio measurement on animals under the condition that the animals are kept awake and can freely move, and meanwhile, the system is not limited by a measurement part.

Disclosure of Invention

The invention aims to provide a system for simultaneously carrying out photoacoustic and electrocardio measurement on an animal in a waking and freely moving state, which improves the convenience of operation and the repeatability of measurement, reduces the infection of the animal, reduces the using amount of a test animal and simultaneously can carry out long-term test observation.

Based on the above purpose, the wearable animal photoacoustic combined electrocardiograph measurement system of the present invention comprises:

A photoacoustic measurement system that measures a photoacoustic signal of an animal;

The electrocardio measuring system is used for measuring electrocardiosignals of animals;

the signal processing system is used for processing the photoacoustic signal measured by the photoacoustic measurement system and the electrocardiosignal measured by the electrocardio measurement system;

a signal output system for outputting the processed photoacoustic signal and the processed electrocardiographic signal;

The system is characterized in that the photoacoustic measurement system comprises a light source system and a photoacoustic detector system, the light source system adopts a pulse laser, the photoacoustic detector system adopts a wearable ultrasonic transducer array system, and the electrocardio measurement system adopts a wearable electrocardio measurement electrode for measurement;

The wearable ultrasonic transducer array system comprises a flexible substrate, an ultrasonic transducer array carried by the flexible substrate and adjustable belt parts extending from the flexible substrate to two sides, wherein the flexible substrate can be bent, the ultrasonic transducer array adopts a curved ultrasonic transducer array, and a photoacoustic detector system consisting of the flexible substrate and an ultrasonic transducer conforms to the curve of an animal part to be measured; the photoacoustic probe system is fixed to the animal body after the bands extending to both sides are combined, the bands may be integrally manufactured and have elasticity, or the bands may be combined at the combining portion, and the combining portion may be a hook and loop portion for length adjustment.

The wearable electrocardio-measuring system is a flexible belt with adjustable length and extending from the flexible substrate, a fixing ring for fixing the electrocardio-electrode is arranged at the tail end of the belt, the fixing ring comprises a variable length part and a fixed length part, and the electrocardio-electrode is arranged at the fixed length part; when the electrocardiogram electrode is used, after the limb part or the ear part of the tested animal passes through the fixing ring, the fixing ring is contracted due to the elasticity of the length-variable part, so that the electrocardiogram electrode is firmly contacted with the limb part or the ear part of the tested animal, and the electrocardiogram measurement is carried out.

Preferably, the pulse laser can emit light with two wavelengths of red light and infrared light, so that the photoacoustic measurement system can measure the blood oxygen saturation of the tested animal.

Alternatively, the photoacoustic detector system and the electrocardiograph measurement system may be provided in the form of a pet garment, the photoacoustic detector system is provided in a main body portion of the pet garment, the electrocardiograph measurement system is provided in limbs of the pet garment, the pet garment worn on a body portion serves as a carrier of the ultrasonic transducer system, carries the ultrasonic transducer array, and the portion worn on the limbs serves as a carrier of the electrocardiograph electrodes, and carries the electrocardiograph electrodes.

Further, the system also comprises a liquid atomization device which atomizes the medicine for treating diseases, so that the animal inhales the medicine during free movement, thereby monitoring the cardiovascular state and the heart function state of the animal after inhaling the medicine.

By the system of the invention, the following effects can be achieved:

(1) The photoacoustic detector system designed by the invention can measure photoacoustic signals of any position in a non-invasive manner, is not limited to a brain, and can reliably contact the position of an animal to be measured no matter which measuring position is used;

(2) The electrocardio measuring system can non-invasively measure the electrocardiosignals of any part of an animal, and the electrocardio electrode can be firmly contacted with the part to be measured, so that the stability of the electrocardio measurement is improved;

(3) the electrocardio measuring system adopts an annular shape and comprises a fixed length part and a variable length part, and the electrocardio measuring electrode is arranged at the fixed length part, so that the annular structure can be firmly contacted with a measured part, and the shape of the electrocardio electrode is not changed;

(4) The pulse laser can emit light with two wavelengths and can be used for measuring the blood oxygen saturation;

(5) The system of the present invention can perform monitoring for a long time because the system is monitored in a conscious and free state, and is used for long-term drug research experiments or life habits and other researches.

Drawings

FIG. 1 is an exemplary block diagram of the system of the present invention;

FIG. 2 is a schematic diagram of a photoacoustic measurement system of the present invention;

FIG. 3 is a schematic diagram of a wearable photoacoustic detector system of the present invention;

FIG. 4 is a schematic diagram of a wearable photoacoustic detector system and a wearable electrocardiograph measurement system of the present invention;

Fig. 5 is a schematic view of an electrode arrangement of the wearable electrocardiograph measurement system of the present invention;

Fig. 6 is a further system block diagram of the present invention.

Detailed Description

fig. 1 is a block diagram of an exemplary system of the present invention, including a photoacoustic measurement system, which measures a photoacoustic signal of an animal to obtain photoacoustic information about the head, abdomen, etc. (depending on the measurement site) of the animal; the ECG measuring system is used for measuring the electrocardio of the animal to obtain the heart function condition of the animal; the signals measured by the photoacoustic measurement system and the signals measured by the ECG measurement system are processed by the signal processing system, and are output by the signal output part through analog-to-digital conversion, denoising, filtering, signal amplification, spectrum conversion and the like, such as outputting a photoacoustic spectrum, an electrocardiogram and the like, so that researchers can further analyze the signals.

Fig. 2 shows a photoacoustic measurement system according to an embodiment of the present invention, where the photoacoustic measurement system includes a light source system, an OPO pulse laser that may employ a pulse laser source, the pulse laser source employs a pulse laser, the wavelength is tunable, the tuning range is 480-960nm, the pulse light source may be connected to an optical fiber bundle or the like as a light guide, the light source is incident on the subject to cause a photoacoustic effect in the subject, the photoacoustic signal is detected by a photoacoustic detection system, and the photoacoustic detection system is an ultrasound transducer array, and may collect an ultrasound signal generated by light absorbed by tissue.

in order to solve the problem that animals carry out photoacoustic measurement in a waking state and a free state, the invention arranges an ultrasonic transducer array in a curved array on a flexible substrate (carrier) which can be folded and bent, carries the ultrasonic transducer array and arranges a flexible PCB on the flexible substrate, the shape can be changed according to the position of the tested animal needing measuring, such as the photoacoustic measurement of the brain, the flexible substrate may be made of flexible material with elasticity, such as a headband, through which the curved ultrasound transducer array and the flexible PCB are carried, if a photoacoustic apparatus of the abdomen or mid-body is to be measured, a substrate in the form of an abdominal belt or a belt, which is elastic, and two ends of the substrate provided with the transducer are provided with belts, and the joint of the two belts is provided with a magic tape or a buckle part (not shown) with adjustable length.

fig. 3 shows a schematic view of a wearable photo acoustic detector system according to the invention, wherein reference numeral 1 indicates a photo acoustic detector system (i.e. an ultrasound transducer system) according to the invention, which is designed to follow the body curve of an animal, is worn by the animal and is freely movable when performing photo acoustic measurements. Further, as shown in fig. 3, reference numerals 2 and 3 denote electrocardiographic measuring electrodes. Two strips can extend out of the base of the photoacoustic detector and can be arranged in a strip manner, as shown in fig. 3, a deformable annular soft part is arranged at the tail end of each strip, an electrocardio measuring electrode is arranged in the deformable annular soft part, when the photoacoustic detector system is worn on an animal, the hind limb of the animal can penetrate through the annular part, and meanwhile, the annular part is tightened at the hind limb of the animal, so that the electrocardio electrodes can be tightly and fixedly contacted with the hind limb to perform stable electrocardio measurement.

As shown in fig. 4, the wearable animal photoacoustic and electrocardiographic measurement system of the present invention is provided, in which reference numeral 4 denotes a band or a buckle portion whose both ends are adjusted. The adjustable measuring device is adjusted through the elastic belt or the buckle part with adjustable length, and can adapt to animals with different sizes and measurement of different animal body parts.

as shown in fig. 5, the wearable electrocardiograph measurement system is a flexible belt with adjustable length extending from the flexible substrate, and the end of the belt is provided with a fixing ring for fixing the electrocardiograph electrode, the fixing ring comprises a variable length part a and a fixed length part b, and the electrocardiograph electrode is arranged at the fixed length part b; when the electrocardiogram electrode is used, after the limb part or the ear part of the tested animal passes through the fixing ring, the fixing ring is contracted due to the elasticity of the variable length part a, so that the electrocardiogram electrode is firmly contacted with the limb part or the ear part of the tested animal, and the electrocardiogram measurement is carried out.

Alternatively, the photo acoustic detector system of the invention may be provided in the form of a pet garment, a garment worn on a body part as a carrier for the ultrasound transducer system, carrying the ultrasound transducer array, a part worn at the extremities as a carrier for the electrocardio-electrodes, carrying the electrocardio-electrodes, whereby the animal may perform photo acoustic and electrocardio measurements in a conscious free state.

as shown in fig. 6, in order to observe the cardiovascular status and the cardiac function status of an animal after inhaling a certain liquid or gas, the system of the present invention additionally comprises a liquid atomization device, the liquid atomization device is arranged in the activity space of the animal, the liquid to be inhaled by the animal, such as anesthetic, liquid of a certain disease, etc., is atomized and then volatilized in the activity space of the animal in the form of gas, and after the animal inhales for a period of time, the reaction of the animal to the medicine can be observed through the measurement result, which is of great significance for pharmaceutical research and animal model establishment. Optionally, when the reaction of the animal in the activity space to the gas or the medicine needs to be observed, the signal processing system controls the liquid atomization device to spray the gas to be inhaled or the atomized liquid medicine in the space, and the time or the time of inhalation is controlled by the experimenter according to the research needs by inputting a signal to the signal processing system through the input device.

During measurement, the pulse laser emits pulse light, the pulse light is absorbed by the small animal body, the generated ultrasonic wave is received by the wearable ultrasonic transducer array, the received ultrasonic wave is sent to the signal processing system to be processed, and the photoacoustic spectrum of the animal is obtained through pre-amplification, AD conversion, orthogonal modulation, time delay and other processing, so that the photoacoustic spectrum is used for observing the cardiovascular state in the animal body. Meanwhile, in order to measure the blood oxygen information in the animal body, the pulse laser can emit light with two different wavelengths, such as red light and infrared light, the light absorption coefficient distribution under different wavelengths is obtained by adopting a dual-wavelength measuring mode, and then the calculation of the blood oxygen saturation is carried out. The photoacoustic signal processed by the signal processing system can be output through the signal output system, such as for display, or further sent to other devices, such as a server for processing.

The signal measured by the electrocardio-electrode is also sent to a signal processing system for processing, and is subjected to pre-amplification, filtering, secondary amplification, band-pass filtering and the like to obtain the electrocardiogram of the animal, and the electrocardiogram of the animal is output by a signal output system, for example, the electrocardiogram of the animal is displayed by a display, or is sent to a server and the like for storage or further processing and the like. For example, the signal output system may simultaneously display the oxygen saturation level of blood in the animal body, the photoacoustic image, and the electrocardiogram through the display so that a researcher can intuitively judge the state of the animal.

Since there is no restriction on the movement of the animal, the device of the present invention allows continuous observation of the cardiovascular status of the animal for a long period of time. Meanwhile, in order to observe the reaction of the animals to certain gases (harmful or harmless) or certain atomized medicines, the medicines can be sprayed or volatilized by an atomizing device in the moving space of the animals, and the reaction conditions of the animals to the medicines are analyzed by continuously observing the photoacoustic spectrum and the electrocardiogram of the animals.

The device of the invention can make the animal simultaneously perform the photoacoustic and electrocardio measurement in a waking and freely moving state, improve the convenience of operation and the repeatability of measurement, reduce the infection of the animal, so as to reduce the use amount of the test animal, and simultaneously can perform long-term test observation.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.