Feasibility Of Image Monitoring For Spontaneous Intracerebral Hemorrhage In The Early Stage With Electrical Impedance Tomography: An Animal Study

Intracerebral hemorrhage (ICH) is one of the most severe medical affairsthat is hardly detected in the early stage. Electrical impedance tomography (EIT),a recently developed technique which can continuously monitor the internalconductivity of an object, may meet the problems of early-stage monitoring ofhigh-risk ICH persons. In this research, EIT studies of physical model ofintracerebral hemorrhage and animal model of ICH were performed to evaluteEIT monitoring the impedance variation within the scalp during ICH or not.Although there were so many efforts were put into investigation of thechanges of impedance of human head, most of them are theoretically or basedon physical models, as well as some other research are focused on assessment ofutility in imaging brain function, few of efforts are put into investigations formonitoring of parenchymal disease. Our team focused on the EIT monitoring ofintracerebral disease for a long time. In this research, we adopted the animalmodels mainly because the animal heads are more similar to human head than physical models not only for tissue character (microcosmic structures andcategory of cells), but also for head structure (macroscopic structures) andcharacteristics of electrical impedance of many kinds of tissues. Before of this,physical model of intracerebral hemorrhage was used to investigate the basicconditions.As ICH will cause changes of impact on the brain and thus result in tissueswelling by the hematoma, it will cause the variation of electrical impedance oftissue, which is depends mainly on the variation of brain shape, volume, cellularstructure and tissue composition. Besides tissue swelling and impedancechanges, ICH can impacts aerobic oxidative respiration of brain cells and lead tocell depolarization that can cause the variation of electrical impedance of tissueeither. Because a cavity of the skull is considered a confined container withconsistent volume, we can hypothesis reasonably that changes in the volume andposition of tissues in specific regions are all in concurrence with impedancechanges which may contribute to the variation of electrical impedance that isdetectable using the EIT method. The hypothesis means that all reasonscontributing to the variation of electrical impedance must be taken into accountto explain the variation of electrical impedance, the reasons include all changesin the scalp such as the changes of local tissue condense; changes of cellularmetabolism, cellular water content, extra-cellular space and changes ofinterstitial fluid component34; changes of tissue (scalp, skull and brain)perfusion, or even the CSF content and moulding.In the current research, when the artery was broken by the collagenase, theblood expanded out of the vessels and formed hematoma in the left side brainand lead to brain dilatancy with increasing pressure. The relative highimpedance hemotoma and the changes of tissues around the hematoma might disturb local impedance while the routine of electric current is increased thatmade the total impedance higher. As for the impedance to CSF absorption, theymight increased obviously too because the CSF content and moulding aroundthe brain changed as significantly as can be detected by EIT at so early stage ofICH. Because it was strongly suggested that the impedance variation is highlyrelated to changes of volume and position of CSF with respect to CSF dynamics,changes of brain ventricle volume must need further experimental investigation.In the total impedance changing procedure of early stage ICH, the role ofmembrane structures (endocraniumdura mater and cerebral pia mater, especiallythe latter one) are other potential facts that maybe worthy further investigations.Although there is a difference between the condense of blood and braintissue, the difference may be not significant that can lead to a positive scanningof CT in the very early stage, for during this period, the blood is mixed with lotof brain debris, and the edema area around the hematoma are still not completed.Based on these assumptions, the negative CT scanning results may be resultedfrom the possibility that in the early stage, the most obvious changes of thetarget area are the impedance changes but not condense changes.In short, there are so many potential reasons contributing to the fluctuatingof impedance around ICH area. Though the actual effect of each reason is stillunknown, the results indicated that by using EIT imaging monitoring technique,we can detect the ICH in a very earlier stage and in a very sensitive mannercomparing with traditional imaging method, CT. Therefore, monitoring ofintracerebral hematoma by EIT method is feasible. Future work is expected tofind reasonable explanations for the difference between time-effects ofchanges of CT and EIT.In conclusion, this study indicates the feasibility and sensitivity of detecting ICH with preliminary EIT imaging on rabbits. Although more specific researchwork should be required before clinical practice, it demonstrates that EIT is apotential method for early detection of ICH and could also be used as a usefuladdition to the pool of tools available today, providing the surgeons early alarmsto rescue patients in time. Part I Real-time2D imaging of physical model of intracerebral hemorrhage withelectrical impedance tomography-----2D imaging trial upon ICH physical modelIntracerebral hemorrhage (ICH) is one kind of the most severe medicalemergence in neurosurgery and early stage detection can lead to good outcomesfor patients. Although electrical impedance tomography (EIT) techniques canmonitor the variation of electric resistance of the cerebrospinal fluidcontinuously, the shunting effect of the scalp and cerebrospinal fluid (CSF)make the current passing through the brain too small to be detected forresistivity changes in the brain. Objective The aim of this research is to build aneasy-made physical model of human head and then testify the feasibility ofmonitoring the ICH induced changes of pressure and impedance by means ofEIT techniques. Methods In a glass-disk, a cardboard was made into a cylinder tomimic the human skull; saline mimic the scalp and CSF; in the cardboardcylinder, a swaybacked agar block was to mimic the brain; and the cardboardcylinder was pasted onto the bottle of the glass-disk with wax to prevent freeflow of saline. Electrodes were fixed around the glass-dick. While the EITmonitoring,50μl,100μl,150μl anticoagulated blood was drop into the shallowdimple to mimic ICH in the brain, and then the anticoagulated blood in thedimple was dipped away by absorbent cotton. To simulate the effect ofhemorrhage pressure that act upon the brain, a dielectric20gram (g),60g,120gplastic balls were placed on the top of the agar block respectively. Results Theresults showed that EIT two-dimensional (2D) images can detect the changes ofelectric resistance of this physical model. The anticoagulated blood can lead tovolume dependent decrease of electric resistance as well as the pressure lead toweigh dependent decrease of electric resistance. Conclusion Although we failed to figure out the reason why the pressure can lead to decrease of electricresistance of this model system, the EIT method was proved a feasible andsensitive method to detect the ICH occurence and development in the earlystage. Part II The establishment of ICH animal modelObjective To establish an experimental animal model for the furtherresearch of EIT monitoring. Methods Sixteen male New Zealand rabbits obtainedfrom the Laboratory Animal Center of the Fourth Military Medical University, weighing2.0-2.5kg, were selected in all experiments. The experimental protocols were approved bythe Ethics Committee for Animal and Human Research of Fourth Military MedicalUniversity. All animals were divided randomly into ICH group and control group. The ICHanimal model protocol was employed. Briefly, rabbits were anesthetized with chloralhydrate (400mg/kg, i.p.) and placed in a stereotactic apparatus maintaining the rectaltemperatures of the animals at37°C. After the hair was cleaned, the skin tissue of centerarea of the scalp was excised to expose area around bregma of skull. To perform acutecerebral hemorrhage, we drilled a tiny hole (diameter is about1.0mm)3mm posterior thebregma and3mm left lateral from the sagittalis suture, left the cerebral dura materundamaged. A glass needle (diameter is about0.3mm) was injected through the cranialholes12mm depth from the skull surface and totally6μ l of type VII collagenase wasinjected within5min while the rabbits in control group were injected6μ l saline. After theglass needle was taken out slowly, the cranial holes was sealed with bone wax immediately.4hours later, the rabbit was sacrificed and the brain was taken out for further checking.Results None blood was found in the subarachnoid space for all subjects, indicating that theICH model was not interfered by subarachnoid hemorrhage (SAH). On the brain tissueslices of the ICH rabbits in the position of injection, obvious hematomas were found in theICH group comparing to no changes in the control group while the brain tissue slices of therabbits in control group were not found abnormal. H&E staining results demonstrate thatextra-vascular RBCs can be seen in the brain tissues only in the injection position of theICH rabbits. These results indicated that the ICH model was successful. Conclusion This animal model is a stable and easy getting method in practice for the ICH research.Part III Feasibility of image monitoring for spontaneous intracerebral hemorrhagein the early stage with electrical impedance tomography: an animal studyObjective The aim of this research is to testify the feasibility of monitoring the ICHby means of EIT technique. Methods Sixteen rabbits were divided into two groupsrandomly (ICH model group and control group). In this research,16electrodes (FMEIT-5)were arrayed equably in parallel pattern in a ellipse circle (3cm long and2cm width) on apanel that has a central hole to permit the crossing of the needle for injection. Theelectrodes were regulated alone by a spring to make them touching the scalp equably. Theconductive gel was painted on the tips of electrodes, and then, electrodes were pushed onthe scalp around the head of the rabbits and electric current of500μ A was injected whilethe variation of electric impedance was monitored for30minutes in advance. Then, to therabbits in the control group, totally6μ l of saline instead of collagenase was injectedfollowing the protocol same to that of ICH model group that described prior at part II. After30minutes,1hour,2hours and4hours EIT monitoring, the rabbits were sacrificed and thebrains were fixed and checked following the protocol of part II. Results All the animalmodels were succeed and the control animals were the same as part II by pathologicalevaluation. The EIT monitoring results showed that all brain EIT images of the rabbitspretreated with collagenase were detected areas with increased impedance17min (5-23min)after injection and the areas increased during the period of monitoring while there werenothing changed for the control group rabbits not only in the EIT images of impedance butalso in the brain tissues. Conclusion The results indicated that EIT (FMEIT-5) is a sensitivemethod to detect ICH in the early stage. Part IV The ICH detective sensitivity comparison betweenEIT (FMEIT-5) and computed tomography (CT)Objective The aim of this experiment was to compare the ICH detectivesensitivity of EIT and computed tomography (CT). Methods Based on thefindings of part III, animals were exposed in the ICH inducing protocol. Tocompare the sensitive difference between EIT and CT (most commonlyemployed method for intracerebral hematoma detecting) in early stageintracerebral hematoma, the ICH rabbits were sacrificed by intravenousinjection of over dose of potassium chloride (KCl) when the EIT imageschanged visibly（about thirty minutes）, and were scanned by CT with aresolution of0.1mm within10minutes after death. After the scanning produceswere finished, the entire brain tissue was taken out immediately and fixed by4%paraformaldehyde for24hours. It allowed us to observe the hemorrhage in theCorpus Striatum directly by cutting the brains into slices (2mm thick) in rabbit’sbrain matrix. After the volumes of the ICH hematoma were estimated by meanof a rough volume formula similar to the measuring methods described byKothari22(volume is length multiply wide and multiply high; the width andheight of a hematoma were measured in the largest hematoma sections, thelength of a hematoma was defined as the number of brain slices that werespanned by the hematoma), pathology checkings (hematoxylin and eosinstaining, H&E) were performed. Results The results showed that all brain EITimages of the rabbits pretreated with collagenase showed areas with increasedimpedance, but we cannot figure out the changes of ICH rabbits by CT scanningmethod. Conclusion The results indicated that EIT is a sensitive method todetect ICH in the early stage, and it may be more sensitive than CT at the beginning of ICH.