| Background and Objective:Intracranial hemorrhage(ICH) is defined as the hemorrhage caused by the rupture of intracranial vascular in brain parenchyma. WHO-MONICA study showed that the incidence of stroke is rising at a yearly rate of 9% in China. Approximately 30% of the stroke patients die and most of the survivors suffer from hemiplegia, aphasia, etc. ICH is the second-largest cause of strokes, which is accompanied by high incidence, high morbidity, high mortality and heavy economic burden. It poses a serious threat to human health and lives, and causes serious economic burden to families and society.Early diagnosis and prompt treatment is the most effective way to reduce morbidity and mortality of ICH. Currently, the common detection methods are used to measure ICH, including computer tomography(CT), positron emission tomography(PET) and magnetic resonance imaging(MRI). However, these expensive devices are not readily available in economically underdeveloped regions. Moreover, these imaging devices have the shortcomings of large size and the inability to provide bedside and emergency on-site monitoring. The magnetic inductive phase shift(MIPS) is an emerging technology, is non-contact, non-invasive, inexpensive, small and able to maintain continuous bedside monitoring, which may become a new tool to detect ICH and to serve as an inexpensive partial substitute to medical imaging.In order to study a wider band of intracranial hemorrhage MIPS and to provide more useful information for measuring ICH, this study presents the magnetic inductive phase shift spectroscopy(MIPSS) detection method. To achieve the objective, this study includes the following two parts.Part I:1. We established the MIPSS detection system, which based on the vector network analyzer(VNA). Utilization Agilent E5061 A RF VNA as the signal generator, the data acquisition unit and the data processing unit of MIPSS detection system. A parallel coaxial single excitation coil- single induction coil(single coil–coil) was designed, which was suitable for measuring the size of rabbit head. The MIPSS detection system with four independent measurement channels, and displaying the data formats of amplitude, phase, impedance, etc. which could not only measure the transmission characteristics of the tissue under test, but also the reflection characteristics of the tissue under test. The measurement frequency range was 300 k Hz- 1.5 GHz, single scan time was 25ms(201 points, IF bandwidth of 30 k Hz) and the phase accuracy of 0.01° to meet requirements of the simulated experiments and the experiments of rabbits with intracranial hemorrhage.2. In order to study the sensitivity of the MIPS detection between the coils and determine the appropriate placement of rabbits, we conducted the test of spatial parameters of coils. In this test, 15 representative points within the coils were selected, and measured the MIPS of these points by injection 4 m L of 0.9% saline. The results showed that at the point closer to the exciting coil or the closer to the edge of the coils, the higher the MIPS detection sensitivity achieved. Considering the factors of rabbit head size and MIPS detection sensitivity, the appropriate point to inject blood into rabbits head was(0, 3, 3) in animal experiments.3. To learn the variation of MIPSS, we conducted a physical model experiment by injection or extraction of Na Cl solutions with different concentrations and different volumes. In this experiment, four Na Cl solutions with different conductivity were prepared, and a simple physical model of two-layer structure was produced. The MIPSS measurements of the physical model were implemented in a frequency range from 1MHz to 1 GHz. The showed that MIPSS value of the low frequency band was smaller while MIPSS value of high frequency band was larger, and the phase shift trends of injection and extraction were opposite. Under the condition of the same volumes, the value of MIPSS had a negative correlation with the conductivity of solutions in the high-frequency band, while the value of MIPSS has a positive correlation with the conductivity of solutions in the low-frequency band. Under the condition of the same solution, the value of MIPSS had a positive correlation with the volume of the solution over the entire frequency band.Part II:1. The four different ICH states were established by the autologous blood injection method in rabbits, including pre-operation, post-operation, blood injection 1 m L and blood injection 2 m L. Thirteen rabbits with four cerebral hemorrhage states were measured using a single coil-coil within a 1 MHz-200 MHz frequency range on the MIPSS detection system. A feature band(FB) with an optimal detection sensitivity and stability within the entire band was determined. To demonstrate the significant difference of MIPSS of the four cerebral hemorrhage states under the FB, a non-parametric statistical multiple comparison rank sum test(Friedman M Test) was utilized for the MIPSS data analysis. Based on the MIPSS characteristics under the FB, we designed a B-F distribution profile to diagnose the severity of cerebral hemorrhage. Experimental results showed that the MIPSS value in low frequency band larger than the MIPSS value in high frequency band for a complex rabbit head. Furthermore, the frequency band with the larger power of S21 was corresponded to the bigger phase shift, which indicated that the sensitivity of the detection system had frequency-dependent properties. The Friedman M Test results showed statistically significant differences among the MIPSS data of the four states of cerebral hemorrhage under FB. And at the characteristic frequency, the average phase shift caused by pre-operation, post-operation, 1m L injection and 2 m L injection were-0.2373°±0.3126°,-0.5031°±0.9257°,-3.4449°±1.4208° and-5.6422°±1.5761°, respectively. The B-F distribution profile was able not only to clearly distinguish the four levels of ICH but also to reflect the overall trends of the ICH of rabbits.2. In order to better verify the ICH model built on rabbits and explain the MIPSS results, MR imaging of the rabbit head was performed, which showed the changes in the cerebrospinal fluid(CSF) of the four cerebral hemorrhage states. CSF MR images acquisition utilized SPACE(Sampling Perfection with Application optimized Contrast using different flip-angle Evolution) sequence to scan 5 rabbits in this experiment. MRI of the rabbit head showed that the CSF changes resulting from injecting blood into the rabbit’s head. With the blood injection volume increased, there was a more obvious decrease in CSF, and the discharged amount of CSF between two consecutive injection states was decreased by a larger volume of blood present in the brain. By utilizing Amira software for image segmentation of CSF, the results showed that the amount of CSF decreased from 1.757 m L to 0.50 m L with ICH states from pre-operative to 2 m L injection blood. Furthermore, we calculated the conductivity value of the whole rabbit brain, and the results showed that the trends of MIPSS under the FB were consistent with the changes of conductivity during the process of brain hemorrhage.Conclusions:1. The MIPSS detection system, which established based on the RF VNA(Agilent E5061A), is capable of operation over a very wide frequency range, with high data acquisition speed and high phase accuracy to meet the requirements of the simulated experiments and the animal experiments.2. The results of MIPSS measurements experiments show that the MIPSS of low frequency band was different with the MIPSS of high frequency band when detection the different objects. These results indicate that the MIPSS results reflect the moisture content of the measured object in high frequency band, while in the low frequency band, the MIPS results reflect the changes of dielectric properties of tissues, cells, and solution of intracellular or extracellular. Therefore, we can conclude that using a high-frequency excitation signal is suitable for measuring water content in the physical model or the lesion, such as cerebral edema or pulmonary edema, and using a low-frequency excitation signal is more suitable for the detection of brain hemorrhage or cerebral ischemia in human or animals.3. The MIPSS results of rabbits brain hemorrhage show that the sensitivity of the detection system has frequency-dependent properties. It should be noted that the MIPS at the characteristic frequency(CF) with the highest detection sensitivity and the greatest stability. This finding suggests that the frequency of the excitation signal is set to the CF of the detection system when biological tissues were measured with MIPS method, which is an effective way to improve the detection sensitivity.4. The MRI results are consistent with the MIPS results in the rabbit experiments, which illustrate the feasibility for measuring ICH of rabbit with MIPSS detection system and the validity of MIPSS results. At the same time, the results illustrate that the MIPSS detection method is able to provide a new possibility for detecting ICH. |
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