CD147, a member of the immunoglobulin superfamily (IgSF), plays fundamental roles in intercellular interactions in numerous pathological and physiological processes. Importantly, our previous studies have demonstrated that HAb18G/CD147 is a novel hepatocellular carcinoma (HCC)-associated antigen, and HAb18G/CD147 stimulates adjacent fibroblasts and HCC cells to produce elevated levels of several matrix metalloproteinases, facilitating invasion and metastasis of HCC cells. In addition, HAb18G/CD147 has also been shown to be a novel universal cancer biomarker for diagnosis and prognostic assessment of a wide range of cancers. However, the structural basis underlying the multifunctional character of CD147 remains unresolved. We report here the crystal structure of the extracellular portion of HAb18G/CD147 at 2.8Å resolution. The structure comprises an N-terminal IgC2 domain and a C-terminal IgI domain, which are connected by a 5-residue flexible linker. This unique C2-I domain organization is distinct from those of other IgSF members. Four homophilic dimers exist in the crystal and adopt C2-C2 and C2-I dimerization rather than V-V dimerization commonly found in other IgSF members. This type of homophilic association thus presents a novel model for homophilic interaction between C2 domains of IgSF members. Moreover, the crystal structure of HAb18G/CD147 provides a good structural explanation for the established multifunction of CD147 mediated by homo/hetero-oligomerizations and should represent a general architecture of other CD147 family members.
The rapid printing of 3D parts with desired electrical properties enables numerous applications. Fused deposition modeling (FDM) using conductive thermoplastic composites has been a valuable approach for such fabrication. The parts produced by FDM possess various controllable structural features, but the effects of the structural features on the electrical properties remain to be determined. This study investigated the effects of these features on the electrical resistivity and resistivity anisotropy of 3D-printed ABS/CB composites. The effects of the process parameters of FDM, including the layer thickness, raster width, and air gap, on the resistivity in both the vertical and horizontal directions for cubic samples were studied because the internal structure of the printed parts depended on those process parameters. The resistivities of printed parts in different parameter combinations were measured by an impedance analyzer and finite element models were created to investigate the relationship between the resistivity and the internal structure. The results indicated that the parameters remarkably affected the resistivity due to the influence of voids and the bonding condition between adjacent fibers. The resistivity in the vertical direction ranged from 70.40 ± 2.88 Ω·m to 180.33 ± 8.21 Ω·m, and the resistivity in the horizontal direction ranged from 41.91 ± 2.29 Ω·m to 58.35 ± 0.61 Ω·m at the frequency of 1 kHz. Moreover, by adjusting the resistivities in different directions, the resistivity anisotropy of the printed parts can be manipulated from 1.01 to 3.59. This research may serve as a reference to fabricate parts with sophisticated geometry with desired electrical resistivity and resistivity anisotropy.
Variations of conductive fluid content in brain tissue (e.g. cerebral edema) change tissue impedance and can potentially be measured by Electrical Impedance Tomography (EIT), an emerging medical imaging technique. The objective of this work is to establish the feasibility of using EIT as an imaging tool for monitoring brain fluid content. a prospective study. In this study EIT was used, for the first time, to monitor variations in cerebral fluid content in a clinical model with patients undergoing clinical dehydration treatment. The EIT system was developed in house and its imaging sensitivity and spatial resolution were evaluated on a saline-filled tank. 23 patients with brain edema. The patients were continuously imaged by EIT for two hours after initiation of dehydration treatment using 0.5 g/kg intravenous infusion of mannitol for 20 minutes. Overall impedance across the brain increased significantly before and after mannitol dehydration treatment (p = 0.0027). Of the all 23 patients, 14 showed high-level impedance increase and maintained this around 4 hours after the dehydration treatment whereas the other 9 also showed great impedance gain during the treatment but it gradually decreased after the treatment. Further analysis of the regions of interest in the EIT images revealed that diseased regions, identified on corresponding CT images, showed significantly less impedance changes than normal regions during the monitoring period, indicating variations in different patients' responses to such treatment. EIT shows potential promise as an imaging tool for real-time and non-invasive monitoring of brain edema patients.
Cerebral edema after brain injury can lead to brain damage and death if diagnosis and treatment are delayed. This study investigates the feasibility of employing electrical impedance tomography (EIT) as a non-invasive imaging tool for monitoring the development of cerebral edema, in which impedance imaging of the brain related to brain water content is compared with intracranial pressure (ICP). We enrolled forty patients with cerebral hemorrhage who underwent lateral external ventricular drain with intraventricular ICP and EIT monitoring for 3 h after initiation of dehydration treatment. The average reconstructed impedance value (ARV) calculated from EIT images was compared with ICP. Dehydration effects induced changes in ARV and ICP showed a close negative correlation in all patients, and the mean correlation reached R2 = 0.78 ± 0.16 (p < .001). A regression equation (R2 = 0.62, p < .001) was formulated from the total of measurement data. The 95% limits of agreement were - 6.13 to 6.13 mmHg. Adaptive clustering and variance analysis of normalized changes in ARV and ICP showed 92.5% similarity and no statistically significant differences (p > .05). Moreover, the sensitivity, specificity and area under the curve of changes in ICP >10 mmHg were 0.65, 0.73 and 0.70 respectively. The findings show that EIT can monitor changes in brain water content associated with cerebral edema, which could provide a real-time and non-invasive imaging tool for early identification of cerebral edema and the evaluation of mannitol dehydration.
Intracranial bleeding is one of the most severe medical emergencies in neurosurgery. Early detection or diagnosis would largely reduce the rate of disability and mortality, and improve the prognosis of the patients. Electrical Impedance Tomography (EIT) can non-invasively image the internal resistivity distribution within a human body using a ring of external electrodes, and is thus a promising technique to promptly detect the occurrence of intracranial bleedings because blood differs from other brain tissues in resistivity. However, so far there is no experimental study that has determined whether the intracranial resistivity changes in humans could be repeatedly detected and imaged by EIT. Hence, we for the first time attempt to clinically validate this by in vivo imaging the influx and efflux of irrigating fluid (5% dextrose in water, D5W) during the twist-drill drainage operation for the patients with subdural hematoma (SDH). In this study, six patients (four male, two female) with subacute or chronic SDH received the surgical operation in order to evacuate the hematoma around subdural region, and EIT measurements were performed simultaneously on each patient’s head. The results showed that the resistivity significantly increased on the corresponding position of EIT images during the influx of D5W and gradually decreased back to baseline during the efflux. In the quantitative analysis, the average resistivity values demonstrated the similar results and had highly linear correlation (R2 = 0.93±0.06) with the injected D5W volumes, as well as the area of the resistivity gain(R2 = 0.94±0.05). In conclusion, it was clinically validated that intracranial resistivity changes in humans were detectable and quantifiable by the EIT method. After further technical improvements, EIT has the great potential of being a routine neuroimaging tool for early detection of intracranial bleedings.
Phantom experiments are an important step for testing during the development of new hardware or imaging algorithms for head electrical impedance tomography (EIT) studies. However, due to the sophisticated anatomical geometry and complex resistivity distribution of the human head, constructing an accurate phantom for EIT research remains challenging, especially for skull modelling. In this paper, we designed and fabricated a novel head phantom with anatomically realistic geometry and continuously varying skull resistivity distribution based on 3D printing techniques. The skull model was constructed by simultaneously printing the distinct layers inside the skull with resistivity-controllable printing materials. The entire phantom was composed of saline skin, a 3D-printed skull, saline cerebrospinal fluid (CSF) and 3D-printed brain parenchyma. The validation results demonstrated that the resistivity of the phantom was in good agreement with that of human tissue and was stable over time, and the new phantom performed well in EIT imaging. This paper provides a standardized, efficient and reproducible method for the construction of a head phantom for EIT that could be easily adapted to other conditions for manufacturing head phantoms for brain function research, such as transcranial direct current stimulation (TDCS) and electroencephalography (EEG).