† Corresponding author. E-mail:
Project supported by the National Natural Science Foundation of China (Grant Nos. 61771448, 61427806, and 51937010), the National Key Research and Development Program of China (Grant No. 2018YFC0115200), and the Natural Science Fund from the Chinese Academy of Sciences (Grant Nos. ZDKYYQ20190002 and YJKYYQ20190005).
Magnetoacoustic tomography with magnetic induction (MAT-MI), as a new kind of in-vivo imaging method, has potential application value in interstitial fluid research. In this paper, we propose the application of MAT-MI with liquid metal serving as a tracer of the interstitial structure to study its fluid behavior, and use it to implement the positional imaging of the spatial distribution of liquid metal. Owing to the particularity of liquid metal magnetoacoustic pressure (MAP) signals, we propose an envelope analysis method to extract the rising edge of the amplitude envelope of the detected waveform as effective position data. And for the first time, we propose the method of superpositing pixel matrix to achieve the position imaging of liquid metal. Finally, the positional imaging of the liquid metal sample embedded in the gel is achieved to have relatively accurate results. This study provides a method of effectively extracting data and implementing the position imaging for liquid metal in the interstitial structure in the frame of MAT-MI.
With the in-depth understanding of the life soft materials, the study of the interstitial structure as a new organ has gradually gained more and more attention. Since De Gennes PG used the concept of “soft matter” for the first time at the Nobel Prize Conference in 1991,[1] several teams worldwide have devoted to the research actively on interstitial structures and their fluid behaviors, trying to reveal the operation law of the interstitial fluid and establish a perfect model describing the life fluid operation system. Preliminary studies have shown that the interstitial structures form a highly efficient communication framework for organisms. The interstitial fluid circulates under the framework to achieve efficient long-distance transport of biological material, energy, and information, the operational characteristics of which are closely related to physiological and pathological conditions and can comprehensively reflect a variety of information about the status of living organisms.[2,3] At present, researchers mainly observe the morphology and distribution characteristics of interstitial structures through anatomical methods,[4–6] which cannot investigate the fluid behavior under living conditions. Fluorescent tracer is an ideal medium for investigating fluid behavior[7,8] and has been widely used in biological fluid pipeline angiography. However, the short development time of fluorescence restricts its application in interstitial fluid research, since the interstitial fluid has a large spatial scale cycle over a large period with the development of new materials. Researchers explore the nanoparticles used as markers to study the behavior of interstitial fluids and obtain initial progress.[9] In-vivo imaging methods have the characteristics of not destroying the life state of living organisms and are an effective method of studying the macroscopic structure and fluid behavior of interstitial tissues. For the physical characteristics of interstitial tissues, imaging methods widely used in disease diagnosis, such as ultrasound, CT, etc., have their limitations in the study of interstitial structures and fluid behavior. For example, the contrast of ultrasound imaging is low for the small difference in acoustic impedance between normal interstitial structures and its adjacent tissue, while CT has the risk of ionizing radiation. The magnetic resonance imaging (MRI) is a new type of in vivo imaging technique with high contrast and good resolution. In recent years, with the in-depth research on functional Magnetic Resonance Imaging (fMRI), the MRI has the function of tracking and imaging the moving fluids.[10] However, MRI equipment is generally bulky and has strict requirements for environmental electromagnetic parameters in its working area, which restricts its application in clinical monitoring of interstitial fluid that moves continuously over a large time span all over the body. Therefore, it is necessary to develop an in-vivo imaging method for the interstitial structure, which can achieve long-term clinical monitoring of interstitial fluid characteristics and systematically study the interstitial fluid behavior.
MAT-MI, as a new type of in-vivo imaging technique, is sensitive to conductivity parameters and has the characteristics of no-radiation, no-contacting, and its imaging that is not restricted by the physical structure of tissues. Since Xu and He from University of Minnesota (USA) proposed the technology of MAT-MI in 2005,[11] researchers have done a lot of work on early tumor detection based on the conductivity difference between normal and diseased tissues, and have achieved a series of results in theoretical research, experimental platforms, and imaging algorithms.[12] Based on the analytical model and the finite element calculation model, the researchers conducted numerical analysis and established a mathematical and physical model of the system.[13–16] Researchers fully demonstrated the parameters of the experimental system and established an experimental platform. On the basics of this, they achieved the experimental studies of physical phantoms and biological tissues, which demonstrated the feasibility and performance of MAT-MI.[17–20] In recent years, the researchers have gradually improved the imaging algorithm to make it more suitable for clinical applications.[21,22] In tumor detection, the conductivity of the lesion area is abnormal and the distribution is unknown. It is necessary to reconstruct the conductivity of the target area and its spatial distribution based on the detected magnetoacoustic (MA) signal and take this as a reference to discriminate and divide the cancerous area.[21–24] Therefore, it requires relatively high spatial resolution and accuracy of reconstructed conductivity of the abnormal area. In the cancer detection in MAT-MI, the demagnetization effect of the induced current can be neglected in the electromagnetic field analysis, and the biological tissue is reduced to a one-way coupled electromagnetic model due to the low conductivity of biological tissues themselves (< 1 S/m). At the same time, the acoustic impedance difference between tissues is usually ignored, and it is regarded as an acoustic uniform fluid, since the acoustic characteristics of the biological tissue including the cancerous area are no more than 10 %, which is much smaller than the electrical conductivity difference ( > 100 %). In the reconstruction algorithm, the unknown conductivity of the tissue is taken as the target parameter. The MA source distribution is reconstructed from the detected MAP of the sample points on the scanning path, and then the spatial distribution of the electrical conductivity is calculated and the precise boundary is reconstructed, which was taken as the reference for cancer screening and its boundary division.
However, in the study of interstitial structure, due to the absence of electrical conductivity abnormal areas of the lesions, the electrical conductivity difference of normal tissues in various parts of the organism is relatively small, which results in the fact that the MA signal is too weak to detect. In order to solve this problem, Zhao et al. proposed the idea of studying the interstitial structure and fluid behavior by using gallium-based liquid metal with high conductivity as the marker and measurement medium in the MAT-MI detection.[25] Galinstan (Quality ratio: Ga : In : Sn = 62.5 : 21.5 : 16) is one kind of gallium-based liquid metal that has good chemical stability and good biocompatibility. Its melting point is –18 °C and has good fluidity and low viscosity at room temperature (as shown in Fig.
The schematic diagram of the MAT-MI detection system for liquid metal in the interstitial structure is shown in Fig.
Taking into account the differences in physical properties between materials, the wave equation of acoustic pressure p can be expressed in the following form:
The MA signal characteristics of liquid metal in biological tissues are significantly different from those in cancer detection because the electromagnetic properties and acoustic properties of liquid metals are quite different from those of biological tissues. Zhao et al. studied the MA signal characteristics of liquid metals with different sizes under a certain symmetrical simplification framework based on the background of MAT-MI, and provided a theoretical basis for the position information extraction of liquid metal.[16] According to the distribution characteristics of liquid metal and the magnetic field distribution of the imaging area, the shape of any slice can be regarded as having a certain symmetry. Therefore, the characteristics of induced current and MAP still satisfy the symmetry relationship described in Ref. [25].
According to the research by zhao et al., the original acoustic wave and the reflected ones coexist due to the reflection and incomplete projection of acoustic waves at the interface between liquid metal and tissue, which results in complex acoustic signal components detected by the transducer at the sampling point. In addition, there are large differences in the detection waveforms of the MAP of liquid metal with different sizes embedded in tissues, which makes it difficult to extract the location information of the liquid metal. In experiment, a narrow-band ultrasonic transducer was usually employed to detect MAP signals. The transducer output waveform is a typical narrowband signal, which can be expressed as follows:
According to Ref. [16], when the size of liquid metal is relatively large, the MAP envelope has multiple peaks, and the first two peaks indicate the two boundaries of the liquid metal along the acoustic wave propagation path, which can be directly extracted to generate a normalized position sequence. Furthermore, the ratio between the amplitudes of the first two peaks on the envelope is 0.55, which is determined by the difference in acoustic impedance between the liquid metal and the biological tissue. The ratio can be expressed as K = 1/(1 + rp), where rp is the reflection coefficient of sound pressure propagating from liquid metal to biological tissue. In this case, the positions of the first two peaks on the envelope can be directly extracted as the boundary information on both sides of the liquid metal. As the size of the liquid metal becomes smaller, the time interval between the MAP waveforms on the two sides of the boundaries decreases, and the waveform overlap gradually increases. When the first peak on the envelope is under the rising edge of the second cluster of waveform envelopes, the two sides of the liquid metal cannot be identified by the envelope. In this case, we need a new algorithm for boundary recognition. When the size of liquid metal is smaller than the half acoustic wavelength in liquid metal under the detection frequency, the detection signal has only one wave cluster due to the waveforms of the two boundaries on both sides almost completely overlapping and the peak of its envelope indicates the position of the liquid metal. In this condition, we will not be able to accurately extract the boundaries on both sides of the liquid metal, but we can extract the position information of the liquid metal by detecting the waveform. Furthermore, under this situation, the liquid metal in the interstitial structure can be attributed to the identification of small targets on a large spatial scale, and our task is to find their spatial location. Taking a cylindrical liquid metal sample with a diameter of 3 mm for example, the typical magnetic acoustic waveform of the transducer t on one slice is shown in Fig.
According to the above analysis, the distance between the transducer and the liquid metal front and between the transducer and the back interface are Rf and Rb respectively. In the Cartesian coordinate system, when the coordinate of the transducer is (xt, yt), the possible regional coordinates of the liquid metal satisfy the following inequality if the directivity of the transducer is not considered:
In the MA image reconstruction, it is necessary to detect sound pressure data through multiple sampling points to achieve the reconstruction of target parameters. In the experiment, multi-point MAP data are sampled through single transducer scans according to a certain regular motion, or transducer array consisting of multiple detection units. If the number of sampling points is n and the position of each sampling point is known as (xit,yit), i = 1,2,3,…,n respectively, the inequality group with n inequalities can be established as follows according to formula (
In multiple points’ sampling, the data quality of some sampling points is relatively poor or invalid sampling for various reasons, which will result in no solution to the inequality group. In order to avoid this problem, in this paper proposed is a method of implementing layer-by-layer superposition of pixel matrix for position imaging. The imaging region is divided into m × n pixel units, and a pixel matrix Ai (i = 1,2,3,…,n) of m × n is defined for each sample point. When the imaging region position (x, y) satisfies formula (
In order to prove the analysis results above, we built an circle scanning MA detection system for experiment as shown in Fig.
The imaging area is a square with a side length of 4 cm, and its center is at the ordinate origin as shown in Fig.
For liquid metal in biological tissues, the conductivity is a known parameter, and the target of imaging is to determine the spatial orientation of the liquid metal without concerning the specific shape of its boundary. So the goal of imaging for each slice is to answer the questions about liquid metal: “yes” or “no”, and “where it is”. Therefore, the number of sampling points can be appropriately reduced to simplify the imaging algorithm and improve the imaging efficiency. The liquid metal position images of 9 sampling points are uniformly arranged on the scanning path as shown in Fig.
The method has potential application value in high-speed dynamic positioning detection of liquid metal for its advantages of small data volume, high calculation speed, and on-line imaging. At the same time, in the parallel detection system using a transducer array, there are fewer requirements for the number of detection units, which is convenient for system installation and integration.
The above results show that the imaging method proposed in this paper can achieve the position imaging of simple targets. In order to verify the universal applicability of the method, we performed this imaging method on a complex planar curved target, which injects liquid metal into the gel channel as shown in Fig.
In this paper, we propose a new method of studying the interstitial structure, which employs liquid metal to mark the interstitial fluid channel and image the liquid metal by MAT-MI to achieve the spatial reconstruction of the interstitial structure. The problem of MAT-MI for liquid metal in biological tissues is attributed to the spatial position imaging of liquid metal. By analyzing the characteristics of the waveform for the liquid metal under a certain size in MA detection, it is proposed that the envelope analysis method be used to solve the problem of data extraction when the multi-reflection waveforms of the MA signal overlap, and the liquid metal position imaging algorithm is designed based on the pixel matrix superposition method. Finally, the columnar liquid metal embedded in the gel is taken for sample, and multi-slice scanning is performed on circle path to collect the MAP signal for reconstructing the positional imaging, and the positional imaging of liquid metal by fewer sampling points is discussed. The results show that the envelope analysis method can effectively solve the problem of liquid metal position information extraction when sound pressure signals overlap, and positional imaging by superimposing the pixel matrix avoides the problem that inequality group has no solution due to unexpected data extraction caused by sampling data failure, which makes the imaging system have relatively high robustness and fault tolerance. Besides, the data extraction and position imaging methods proposed in this paper are equally applicable to the spatial position reconstruction of conductive objects of other known materials. The MAT-MI technology with high conductivity fluid material as its detection object and tracer is an effective method of studying the circulation characteristics of interstitial fluid in biological tissues, which provides a new feasible method of studying the restricted space material transmission and information connectivity, and may provide new experimental basis for scientific explanation of TCM meridian theory. Furthermore, this position imaging method also has a certain application value in the position detection for known conductive material such as underground buried cable or metal pipe and other subjects.
In this study, the organism is simplified into a uniform fluid, and the liquid metal into a spatial linear structure without considering the influence of the complex structure of the organism. However, in the actual organism, there are bones and lung structures, as well as gas and other substances in the body cavity, the acoustic characteristics of which are quite different from soft tissues. In the future research, it is necessary to systematically study its influence on sound field propagation to improve the accuracy of signal extraction. The morphology of the interstitial structure in different parts of the body is quite different. For example, the interstitial of the extremities is approximately columnar or linear, the interstitial of the adventitia has a hollow tubular structure, and the interstitial of the trunk is closer to the sheet. Therefore, it is necessary to design different transducer arrays for the interstitial shape characteristics of different positions and the limb structure of the corresponding parts. Besides, under different physiological and pathological conditions of organisms, the fluid channel of the interstitial structure may appear to be “bifurcation”, so it is necessary to consider the positional imaging problem of multiple liquid metal wires in the detection space. In addition, the spatial resolution of this imaging method is similar to the resolution of ultrasound imaging, which is about half the wavelength of the acoustic wave at the detection frequency. The detection target of the interstitial structure position is the target with a small size on a large space scale. Under this framework, the recognition efficiency of small size target needs improving. This is related to the strength of the excitation system and the sensitivity of the detection system, which can be achieved by optimizing the system parameters.