A Method And Experimental Study On The Real-Time Continuous Monitoring Of Cerebral Edema For Rabbits Based On Magnetic Induction Phase Shift

Cerebral edema,a very common secondary disease after traumatic brain injury(TBI)or stroke,can cause the increment of brain volume and intracranial pressure(ICP).If appropriate interventions were not timely operated,ICP will continue rising,even cause brain displacement and hernia,and result in life-threatening.Therefore,real-time monitoring of edema is of great significance for improving the therapeutic condition of stroke or TBI,and reducing the mortality and disability rate.At present,invasive ICP monitoring and imaging methods are two ways commonly used for the detection of cerebral edema.Although invasive ICP monitoring can do real-time observation of the development of edema,it will cause additional pain even infection which aggravates the condition.Other imaging methods such as MRI,CT and PET can get rich information about the development of edema by craniocerebral imaging without invasion.However,these kinds of imaging equipment which are too large and usually set fixed,cannot do real-time monitoring and also have low detection time resolution,thus running the risk of delay in diagnosis.Magnetic induction phase shift(MIPS)is a new method to detect the dielectric properties of biological tissues,which is to use the excitation signal of a certain frequency generated by an excitation coil to generate a main magnetic field in the biological tissue,which will produce an eddy current in the tissues and form a disturbing magnetic field.The intensity of the disturbing magnetic field is related to the structure and physiological state of biological tissues.MIPS with advantages of non-invasiveness,non-contact,strong penetration and small size is expected to become an effective method for continuous bedside monitoring of cerebral edema.However,due to low dielectric properties of biological tissues,MIPS detection suffers from low sensitivity and poor stability.In this work,in order to improve the sensitivity of MIPS detection and explore its feasibility in non-invasiveness,non-contact,real-time and continuous monitoring of cerebral edema,the magnetic induction phase shift spectrum(MIPSS)detection method is proposed based on MIPS correlation theory.Then a real-time and continuous monitoring system for cerebral edema with high sensitivity and stability was established.Meanwhile,over a longer period of time(24 hours),experiments of continuous monitoring of cerebral edema in animals(rabbits)were carried out.The main work includes the following aspects:1.The theory and simulation study of MIPS for the detection of cerebral edema.Firstly,to provide a theoretical basis for studying the relationship between MIPS and cerebral edema,a three layer spherical brain model of conductivity was established so as to deduce a basic theoretical relationship between the increase of brain volume and the change of MIPS.Secondly,the MIPSS detection method was put forward based on the basic principles of MIPS technology,biological tissue conductivity spectrum characteristics and transmission line correlation theory.This method can get richer cerebral edema information and provide theoretical guidance for improving the sensitivity of MIPS.Thirdly,through the analysis of the mathematical model of MIPSS,it was found that the phase difference of MIPSS between the excitation signal and the detection signal can represent the information of cerebral edema.Finally,based on the three layer conductivity brain model and the coaxial single excitation-detection coil,the electromagnetic simulation experiment of MIPSS for cerebral edema detection was carried out,the result of which shows that the MIPS at each frequency point of MIPSS decreases with the increase of the volume of the simulated brain parenchyma,which is consistent with the theoretical deduction.Also,within certain range,the sensitivity of MIPS increases with the increase of frequency.2.The establishment of a real-time continuous MIPSS monitoring system for cerebral edema.Firstly,through the analysis of the basic structure,function and main technical indexes of the magnetic induction brain monitor developed by this research group,it was found that it met the basic needs of MIPSS measurement.According to the theoretical relationship between MIPSS and cerebral edema and the principle of MIPSS measurement,the method of MIPSS measurement for cerebral edema is proposed.Secondly,a coaxial single excitation-detection coil with reasonable layout was designed,which accorded with the MIPS theory and matched the size of the experimental animal head(rabbit).Through the no-load impedance matching measurements,the excitation signal frequency with the best basic matching of the monitoring system was found.Meanwhile,through the sensitivity measurements of the different space positions of the coil,the placement of the head of the rabbit in the animal experiment was determined.Next,in order to meet the experimental needs of long time,real-time and continuous monitoring,the real-time continuous monitoring software for cerebral edema with the functions of automatic MIPSS measurement parameters setting,real-time continuous acquisition of MIPSS data and real-time display of MIPS change was designed.The establishment of a real-time continuous monitoring system for cerebral edema provides an important technical support for improving the sensitivity of MIPS detection and realizing non-invasiveness,non-contact and real-time continuous monitoring of cerebral edema.3.Experimental study on continuous MIPSS monitoring of cerebral edema.The MIPSS was continuously measured while the simulated brain parenchyma solution(?=0.292S/m)was slowly injected into the container of the simulated rabbit head.Consequently,the results showed that with the increase of the volume of simulated brain parenchyma solution,there are 3 frequency points presenting sharping change.By analyzing the characteristics of the change of the 3 frequency points MIPS and the characteristic of impedance matching,the frequency point with the optimal sensitivity of the MIPS detection was basically determined(75.22578MHz).After analyzing the current animal models of cerebral edema,the rabbit frozen induced edema model which can better simulate traumatic cerebral edema was chosen as the main object.Moreover,24-hour continuous monitoring of MIPSS in rabbit showed that the best frequency band of MIPSS detection for cerebral edema is from 300 kHz to 75 MHz and there were 4 frequency points in MIPS which had obvious changes over time.By analyzing the MIPS variation and impedance matching characteristics of the 4 frequency point,and combining related theories,it was found that the frequency point with optimal sensitivity was 64.14396 MHz under rabbits experimental conditions.The monitoring system can collect and display the MIPS changes at any frequency in the frequency band of the excitation signal in real time.This finding lays a solid foundation for realizing real-time and continuous monitoring of high sensitivity MIPS in real sense.4.Animal experimental study on the relationship between cerebral edema,MIPS and brain water content(BWC).The theoretical relationship between edema and MIPS and BWC deduced the basic relationship between the amount of BWC enlargement and the change of MIPS,providing the basis for the study of the relationship between cerebral edema and MIPS and BWC.The rabbit cerebral edema model was established by the method of external cranial cryopreservation.Under the detection frequency of 64.14396 MHz,real-time MIPS monitoring was conducted in the experimental group for 2 hours(n=10),6 hours(n=10),12 hours(n=10)and 24 hours(n=10)respectively,after which 4 groups of BWC values were measured by using dry and wet weighing method.Meanwhile,after real-time MIPS monitoring the rabbits in control group(n=8)for 24 hours,1 group of BWC values was measured as a contrast.By analyzing the MIPS signal of real time monitoring for 24 hours in rabbits,it was found that the MIPS of the rabbits in the experimental group had a significant change with time which showed a decline trend.As a contrast,in control group,MIPS showed no obvious increase or decrease and the change was not significant.5 groups of MIPS and BWC data showed that within 24 hours after cryopreservation,BWC increased gradually and,at the same time,the amount of MIPS changes was also increasing.The above results showed that the change of MIPS in the experimental group was caused by the enlargement of the volume of brain parenchyma caused by cerebral edema.BWC and MIPS statistical results indicated that MIPS can not only effectively monitor the pathological reaction of cerebral edema caused by the expansion of brain parenchyma,but also can effectively distinguish the cerebral edema of different severity according to the extent of the volume expansion of the brain parenchyma.The correlation analysis between MIPS and BWC showed that MIPS and BWC have a significant linear correlation,consistent with the theoretical derivation.Also,through linear regression analysis,the basic relational type between MIPS and BWC was obtained,thus providing a reference for MIPS to become a non-invasiveness,non-contact and real-time monitoring method of BWC.By analyzing the pathological process of cerebral edema and the changes of MIPS,it was found that MIPS detection of BWC has higher sensitivity in the acute onset of cerebral edema,which is of great significance for the early diagnosis of cerebral edema.5.A real-time synchronous MIPS and ICP monitoring of cerebral edema in rabbits for 24 hours.The basic relationship between cerebral edema and MIPS and ICP respectively indicated that the changes of ICP and MIPS are both related to the increase of brain volume.The compensatory mechanism of the cerebrospinal fluid(CSF)and the cerebral blood flow(CBF)in the process of ICP elevation shows different characteristics of MIPS and ICP in different stages of the expansion of the brain parenchyma.The rabbit brain water model was established by cryosurgery outside the skull.The Camino intracranial pressure monitor and the real-time continuous monitoring system of cerebral edema were used to synchronously monitor the MIPS and ICP of the experimental group(n=20)and the control group(n=12)for 24 hours in real time.By analyzing the characteristics of the 24-hour ICP and MIPS change rates and amplitude of changes,combining the basic theoretical relationship between cerebral edema and MIPS and ICP,the CSF compensatory,the CBF compensatory and the decompensated period of ICP rise caused by cerebral edema because of cranial freezing were determined.The MIPS and ICP statistical results showed that MIPS was able to detect cerebral edema 3 hours earlier compared with the traditional invasive ICP monitoring method,which is of great significance for early detection of cerebral edema,early intervention,improvement of treatment level and outcome of prognosis.The correlation analysis between ICP and MIPS showed that there was a significant negative correlation between them,which was stronger in CBF compensatory period.However,ICP and MIPS showed quite different characteristics in the CSF compensatory period and decompensated period,indicating that the negative correlation is nonlinear.The nonlinear regression analysis between MIPS and BWC showed that in the process of the increase of ICP caused by cerebral edema,the ICP increased exponentially with the exponential decline of the decrease of MIPS,and this relationship was more intense in the period of CBF compensation.This discovery is expected to provide a safe and effective real-time monitoring method for ICP.