Mobile charges exist in biological tissues in the form of ions, ionic groups, and electric dipoles. Biological tissues can be viewed as a combination of electrical resistance and capacitance. The electrical conductivity of biological tissue is its biological property, and different pathophysiological states have different electrical conductivities. The contents of various tissues in the skull are in dynamic balance. Once a certain lesion occurs in the skull, the intracranial conductivity also changes accordingly. Therefore, changes in intracranial conductivity can be used to determine whether the brain tissue is affected.
In this study, the intracranial conductivity significantly increased during the acute phase of TBI. This is similar to the increase in blood conductivity of abdominal subcutaneous injections in rabbits monitored by Chen et al. in 2020 (Chen et al., 2020). It is also similar to the use of EIT by Xu to monitor the increase in conductivity of intracranial blood injection in a pig model (Xu et al., 2010). However, the pathophysiological reaction after TBI in a closed cranial cavity is more complex. When TBI occurs, the blood vessels in the subarachnoid space, pia mater, and cerebral parenchyma are ruptured, and the outflow of blood accumulates in the subarachnoid space, pia mater, and brain parenchyma to form an intracranial hematoma, which may be simultaneously accompanied by subarachnoid hemorrhage. When a TBI occurs, it leads to local brain tissue injury and cell rupture, resulting in intracellular fluid outflow coupled with increased intracranial pressure, insufficient blood perfusion, swelling of unruptured nerve cells and glial cells, and tissue cells around the injury area, resulting in vasogenic and non-vasogenic brain edema. We know that at 21 MHz, the electrical conductivity values of cerebrospinal fluid, blood, gray matter, and cranial white matter are 2.0096, 1.1435, 0.38132, and 0.20583 S/m, respectively (Hasgall et al., 2012), whereas the conductivity of edema tissue after TBI will be higher than that of normal tissue (Harting et al., 2010), and the electrical conductivity of blood will be higher than that of brain parenchyma and edematous brain tissue; therefore, intracranial conductivity continues to increase.
The animal model used in this study strictly ensures that the dura mater of the animal remains intact during the occurrence of traumatic craniocerebral injury, that is, to ensure that the cerebrospinal fluid is not artificially drained. The aim is the restoration of intracranial physiological and pathological conditions after craniocerebral injury. In the closed cranial cavity, cerebrospinal fluid has the highest intracranial electrical conductivity (Rojas et al., 2008) and exists in large amounts in the brain. In a previous study, our team established a three-dimensional craniocerebral simulation model including the scalp, skull, cerebrospinal fluid, brain parenchyma, ventricle. MIT was used for monitoring. This study shows that MIT can image and locate the location of intracranial injury after TBI (Zhang et al., 2021). In the present study, the intracranial pressure increased following craniocerebral injury in rabbits, and the compensatory mechanism for intracranial pressure began. When the local intracranial pressure increased, the local cerebrospinal fluid and arterial blood perfusion decreased and reflux increased, resulting in a decrease in cerebrospinal fluid in the intracranial local sulcus gyrus. This is combined with the increase in electrical conductivity caused by local cell fragmentation and intracellular fluid overflow, as well as the increase in local electrical conductivity caused by the increase in edematous tissue and the formation of intracranial hematoma. In this study, the change in electrical conductivity was divided into two stages. In the first stage, the electrical conductivity changes rapidly within 20 min after the occurrence of TBI, mainly due to the increase in intracranial hematoma, formation of brain edema, and increased cell fragmentation. During the second stage, 20 min after the occurrence of TBI, the change in electrical conductivity decreased significantly, partly due to the decline in the increase of electrical conductivity caused by hematoma, edema and cell damage, and partly due to a reduction in local cerebrospinal fluid caused by increased intracranial pressure. This is consistent with the results reported by Yang et al. on magnetic induction phase shift that showed that the maximum mean phase shift was the turning point of hemorrhage from the acute phase to the chronic phase 20 min after head injury (Chen et al., 2017).
The advantage of using the CCI rabbit model to simulate TBI in this experiment is that the mechanical factors, such as the impact time, speed, depth, and number, can be controlled, and this method has high repeatability. We report the first use of multiple impact head injury. Experiments revealed that the two degrees of TBI injury differ significantly and the head injury in this animal model is closed; that is, the dura mater remains intact and intracranial hemorrhage occurs.
Because of the circular arrangement and circumference of the MIT sensor array, the forward model is used as the standard circular domain in this study. Compared with EIT, a forward model with an accurate boundary shape must be built, and MIT shows its advantages. In addition, because differential imaging is used in this study, the accurate prior information of conductivity distribution need not be known. The MRV used in this study, that is, the average reconstruction value of the ROI in the reconstructed image, can only be obtained by selecting the ROI after MIT was used to obtain the reconstructed image.
In this study, we used two or three impacts to simulate different degrees of TBI. Tissue staining revealed that the maximum bleeding areas in the brain tissues of the two models differed significantly. It is noteworthy that the normalized MRVs obtained using MIT monitoring continued to increase, the linear regression coefficients exceeded 0.98, and the slope of the linear regression was statistically different. We observed that MIT monitoring can distinguish between different degrees of TBI. Interestingly, in the two TBI models, the rate of conductivity change in group A was greater than that in group B; however, the degree of brain injury in group A was lower than that in group B. When severe TBI occurs, the local intracranial pressure changes drastically, the local tissue undergoes cell rupture, necrosis occurs, and tissue edema become heavier, and the compensatory mechanism of cerebrospinal fluid and blood flow appears early (Wykes & Vindlacheruvu, 2015).
Although the intracranial pressure may change after head injury, exhibiting a certain relationship with the change in conductivity, an intracranial pressure monitoring device was not used in this study due to the nature of the conditions. We used a closed head injury model, and the intracranial pressure monitor requires the dura to be opened and a probe implanted. This could cause loss of cerebrospinal fluid and affect the mechanism of intracranial pressure compensation after a closed head injury. Although the skull was opened in this model, the dura mater was kept intact and an airtight cranial state was maintained throughout. In the aspect of location, because the MIT instrument used in this study is limited by the size of the hardware system, the monitoring range is large, and the rabbit brain is very small. Therefore, the instrument does not match the animal and therefore cannot clearly reflect the accurate location of brain injury in the tested animals. However, if a real human body is used, it can better adapt to the size of the MIT hardware system as the brain is larger. In theory, it will achieve better imaging results than those obtained using experimental animals. Although the human spinal fluid layer will be thicker, previous simulation studies performed by our group show that better imaging can be performed even in the presence of cerebro-spinal fluid(Zhang et al., 2021). The imaging in this study is based on two-dimensional imaging, which mainly reflects the changes in electrical conductivity of the plane where the coil is located. Indeed, full-scale three-dimensional imaging can be more conducive to accurate diagnosis in theory, but because of the extremely poor conditioning of the MIT reconstruction image itself, achieving accurate three-dimensional imaging is difficult.
In addition, this is the first preliminary study of MIT for early monitoring of TBI to our knowledge. Only two injury models were constructed in this study, which can only verify that MIT can identify TBI with different levels of injury. The relationship between the changing trend of the MIT's MRVs and the degree of brain damage requires further evaluation. It is hoped that the degree of brain damage can be inferred via real-time monitoring of changes in MRVs of MIT, and that MIT could be used for long-term continuous monitoring of TBI.