Clinical Research Of Contrast-Enhanced Delay Scanning Of Spiral CT Quantification Of The Hepatic Fractional Extracellular Space

THE RESEARCH PURPOSE AND SIGNIFICANCE:The concept of liver fibrous hyperplasia disease is put forward the famous hepatologist Hans Popper in 1984. It is now known liver fibrosis is a group of clinical pathological syndrome, effect of various body internal and external pathogenic factors, which can lead to abnormal and excessive extracellular matrix hyperplasia and deposition, and the pathology change of excessive collagen deposition dominated, causing vascular compression microcirculation perfusion decrease, further development may cause of portal hypertension and liver fatty degeneration and necrosis, and finally become the irreversible hardening. Therefore, liver fibrosis is of all kinds of liver damage cirrhosis common and basic links of steering. With the development of liver fibrosis mechanism of in-depth study, at present researchers have confirmed that part of hepatic fibrosis or early cirrhosis is irreversible, therefore carries on the early diagnosis, staging of liver fibrosis is very important.Liver biopsy is considered" the gold standard for diagnosis of liver fibrosis ".Based on liver biopsy specimens of continuous slice and staining can determine liver lobules, inflammation, fibrosis change range. But the test is an invasive invasive examination, only static evaluation generally on liver fibrosis, difficult to be repeated to evaluate fibrosis progression and response to treatment, and differences were observed between the sampling error, in addition to the technology are unavoidable in biopsy specimens from patients, so more and more scholars begin to question their accuracy and clinical practical value. For noninvasive method can be repeatedly used to evaluate the degree of liver fibrosis has been the hot spot, the difficulty of research in recent years.The technique of ultrasonic, CT, MRI and other imaging has been an important means of noninvasive evaluation of liver fibrosis, in recent years to carry out CT, MRI functional imaging, such as elastic imaging has gradually become the research hotspot. Ultrasound, CT and routine MRI can display changes in liver morphology, but not sensitive to early diagnosis of fibrosis, also cannot be accurately graded for the degree of fibrosis. The changes of vascular structure distortion of contrast-enhanced ultrasound is better than the simple Doppler ultrasound observation result in fibrosis and related hemodynamics, grading the degree of fibrosis, but in numerical selection and Quantitative Ultrasound Hemodynamics there is no consensus. Perfusion imaging can reflect the blood supply of organs, tissues and hemodynamics in hepatic microcirculation level, more research thinks, portal vein perfusion of hepatic fibrosis and hepatic artery perfusion decrease increase can differentiate mild fibrosis and moderate fibrosis. However, perfusion imaging of the liver only a certain level, can not make a comprehensive study of the whole liver, and the mathematical model of quantitative perfusion imaging and there is no uniform standard, there is a large difference between the results of different income perfusion model, in addition to perfusion imaging in scanning on patients affected by factors (breathing exercise, hepatic congestion, inflammation, etc.) more, and radiation has a certain CT perfusion and MRI perfusion scanning imaging is slow. Elasticity imaging (Elastography) is the use of liver tissue elasticity by exogenous changes after vibration to speculate on the extent of liver fibrosis, the imaging findings with histological staging has good correlation, but the elasticity imaging measurement is fibrosis caused by liver stiffness change, rather than the fiber itself, so the other liver stiffness change caused by non liver fibrosis disease (heart failure, acute inflammation, portal hypertension, liver congestion, cholestasis etc.) can have a greater impact on the results.Effect of additional ultrasound elasticity imaging also by factors such as obesity, abdominal effusion. The use of diffusion weighted magnetic resonance imaging (DWI) on the diagnosis of liver fibrosis are carried out, most of the current study that hepatic fibrosis due to reduce the increase of fibrous connective tissue and blood flow, leading to apparent diffusion coefficient (ADC) decreased, there were significant correlation with the degree of fibrosis and its ADC value, but for the choice of the scanning parameters and b values choice there is no uniform conclusion, and also the limitations of the more obvious the existence of DWI, the accuracy of factors such as iron deposition, fatty degeneration have influence on the result. Recently some scholars put forward the concept of standardization of ADC value is ADC/ADC, liver spleen, think that the standardization of ADC value can reflect the degree of liver fibrosis, and the repeatability is better, however, its clinical application needs further confirmed. Magnetic resonance imaging (MRS) is also commonly used research methods of hepatic fibrosis grading, clinical on commonly used 1H spectroscopy and 31P spectroscopy. So far, many research conclusion suggest that MRS may be a potential tool for the staging of hepatic fibrosis, there is still much controversy regarding the relationship between the spectroscopic results and pathological change. Other MRI technologies such as magnetization transfer (MT), diffusion tensor imaging (DTI), T, p-MRI imaging studies applied to the staging of hepatic fibrosis were also reported in the literature, but due to the limited number of samples and other factors, its value is not clear.Generally, there are 3 kinds of gap in the liver histologically, namely endovascular gap (intravascularspace, IVS) space, intracellular (intracellular space, ICS), extracellular extravascular space (extravascularextracellular, space, EES). The essence of liver fibrosis is the expansion of collagen and matrix protein deposition causes EES. Normal EES accounted for about 15% of the liver solution space, but in hepatic fibrosis EES proportion can be more than 50%. Varenika and other scholars established in 4 liver fibrosis model rats and contrast enhanced CT scan with CCI, through the hepatic parenchymal enhancement degree relative blood pool degree of enhancement ratio calculated liver extracellular space size (extracellular space, ECS, EES and IVS by common component), the research results showed that the Ishak ECS size and liver fibrosis has an obvious positive correlation (R 2=0.751, P<0.01), so this method can be used for quantitative assessment of hepatic fibrosis in rat liver fibrosis degree. Subsequently, Zissen et al also confirmed through clinical cases that a group of traditional water-soluble iodine contrast agent intravenous injection after a period of time to reach the balance between EES and IVS distribution and not be hepatic uptake into IVS, namely hepatic CT enhancement scanning of "balance", the real quality enhancement during this period, liver indirectly reflect the contrast agent in hepatic extracellular space (including IVS and EES) distribution; and thus to assess the early liver fiber. The study showed normal fECS accounted for a total of 15% fluid space, while in the patients with cirrhosis can exceed 50%.This paper attempts to further clinical study based on the animal experimental study, by using the principle of traditional water-soluble iodine contrast agent in hepatic cells can outside the vascular space outside the gap and intravascular reach equilibrium without entry clearance in hepatic cells, with enhanced spiral CT scan technology, through the hepatic parenchymal enhancement degree relative blood pool strengthen the extent of the ratio calculated liver extracellular space size (including the extravascular extracellular space gap liver and blood vessel), thus early diagnosis and quantitative assessment of hepatic fibrosis. The purpose of this study is mainly to confirm the crowd normal patients and patients with liver fibrosis of the liver extracellular space differences do exist, its significance lies in through this simple, reproducible, noninvasive examination method for quantitative assessment of hepatic fibrosis staging, and make early clinical diagnosis, to provide an objective basis for the imaging clinical on liver fiber early treatment, evaluation of therapeutic effect and prognosis; Especially in our country, the majority of carriers of hepatitis B virus or infected, this simple and practical check can play an early screening purposes, having an important significance to prevent or delay the occurrence of liver cirrhosis.MATERIALS AND METHODS:1. Materials and methods1.1 The object of study:Selection of 32 adult patients with acceptable urography examination (no previous history of liver disease) and 32 cases of hepatic fibrosis. All the patients had no obvious without fatty liver, intrahepatic bile duct dilatation, liver tumor history, had not received systemic chemotherapy or radiotherapy, no blood system diseases. Hepatic fibrosis group case selection should include chronic hepatitis B history of 5 years, at the same time with abnormal liver function tests of serology. All patients selected were consistent with the requirements of the medical ethics committee and signed informed consent..1.2 CT examination:Using PHILIPS 64 row spiral CT scanner Brilliance. Select the 120kV conventional scanning tube voltage, tube current was 200-300mAs, Philips dynamic dose dispensing technology using controlled tube current (Dynamic Dose Modulation, DOM) automatically adjust the tube current, increase the signal in the thicker parts, in thinner or gas parts reducing signal, in the same circle process, according to the change of the same site in patients with different projection angles of absorption rate, real-time dynamic adjusting ray dose. Other conditions were the same scan groups (position:according to the condition of patients with upper limb artery choose the most comfortable position, lower extremity arterial the hands at the head of the supine position). Collimator combination:64* 0.625mm; scanning field: 350mm; thickness:0.75-2mm, reconstruction interval:0.5～1mm; pitch:0.65. Image acquisition is transmitted to Extended Brilliance Workspace workstation for postprocessing, the thickness of 5 mm,5 mm away from the layer. Contrast with Omnipaque 350mgl/ml, total 80ml, injection rate 3ml/s. After injection of contrast agent 25s,60s,10 minutes for enhanced scan.1.3 Liver puncture biopsy:In B ultrasound guided percutaneous liver puncture, puncture site in the anterior axillary line eighth,9 or ninth intercostal axillary midline,10 intercostal space, by firing type spring biopsy needle, the liver tissue of 2,1.5 cm long, fixed in 10% neutral formalin solution, embedded in paraffin, tissue 3-4 mu m thick continuous section 6, required to observe 6 portal. Section staining:hematoxylin staining:hematoxylin eosin (HE) staining; Masson staining; staining; D-PAS staining. Immunohistochemical staining:CK7; CK19; heat shock protein (ubiquitin); immunofluorescence:hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg).1.4 Image analysis and data processing:1.4.1 Quantitative analysisSeparately by two radiologists to scan and delayed enhancement scanning image measurement, measurement results have differences, average both. ① Hepatic parenchymal enhancement degree (L) measurement of the left lobe of liver: selected two circular region of interest (region of interest, ROI, about 1cm2) measuring its enhanced liver CT value, L=Lpost-Lpre. Select the region of interest should be distributed area to avoid major blood vessels in the liver (distribution area and observe the main vascular mainly based on 60S scans of the same size); Area. ②Blood pool enhancement degree measurement:three levels of abdominal aorta in different measuring the enhancement of CT value before and after, with ROI, A=Apost-Apre. ③Liver extracellular space (fECS) assessment:fECS=L/A* (1-Hct), Hct for hematocrit[1].1.4.2Statistical analysisAll data packets by using SPSS18.0 statistical software, count data using chi square test, normal distribution variance, the measurement data using two independent samples t test, with the pathological diagnosis as "gold standard", by drawing the ROC curve to evaluate the value of fECS diagnosis of hepatic fibrosis. A statistical test for the level of alpha=0.05.RESULTS:2.1 Pathology of hepatic fibrosis group stage and microscopically (staging criterion referenced "chronic hepatitis B prevention guide" 2010 Edition)8 patients with stage S1:including portal, portal area fibrosis and localized perisinusoidal fibrosis or interlobular fibrous scar, two shall not affect the integrity of the lobular structure.8 patients with stage S2:bridging fibrosis, although the fibrous septa formation, but most still retain the lobular structure.10 patients with stage S3: note the amount of fibrous septa, separating and destruction of hepatic lobules, disturbance caused by lobular structure, but there is no cirrhosis.6 patients with stage S4:liver parenchyma extensive damage, diffuse fibrous hyperplasia, liver cells were separated in different degree of regeneration and false lobule.2.2 The normal group and the different pathological stages of hepatic fibrosis in patients with hepatic extracellular space parameter.In this study, through a comparative study of the normal group and hepatic fibrosis group were two sets of data, the study found similar results with Zissen et al. The fECS normal group is 0.298+0.056, hepatic fibrosis group fECS was 0.369+ 0.059, t test was used in the two sets of data, the P value is less than 0.05, thus confirming the normal group and hepatic fibrosis of liver extracellular space the size of the set difference. At the same time, refer to the pathological grade classification standard, ROC curve analysis of the obtained data, found that fECS=0.308 as a group and fibrosis group may cut the control, when fECS>0.308, it prompts may have occurred in liver fibrosis. Zissen et al in the screening process of the hepatic fibrosis patients, included in the standard is according to clinical MELD integral, serum creatinine, bilirubin, INR and other indicators of the use of points, easily affected by non liver disease factors, directly affect the judging the severity of liver fibrosis real, in accuracy and pathological results of the existence of [2] large differences.And the integral is often used for evaluation of end-stage liver disease, is not sensitive to early liver fibrosis. The study of hepatic fibrosis group into the standard is the use of biopsy results as the "gold standard", the collected data is more accurate, the results are more reference value. Of course, in the course of this study selected cases, also need to exclude the effect of hepatic fat deposition, intrahepatic biliary dilatation, renal excretory insufficiency and anemia and other factors. The control results of pathological grade,32 cases of liver fibrosis in patients with existing (8 cases, stage S18 cases, stage S2 10 cases, stage S3 6 cases of stage S4) corresponding to the fECS were 0.311,0.322,0.326,0.395, and the pathological grading the corresponding fECS mean differences of ladder type. But due to the sample number limitation, the set of values is influenced by individual factors, there may be a large error; In the following research, based on abundant case data, we will further explore the relationship between fECS and pathologic grading of liver fibrosis in patients with size, and tried to find out early, boundary value, advanced liver fibrosis.CONCLUSION:Enhanced spiral CT scanning can delay of liver extracellular space (fECS) of the size of the quantitative evaluation, through the comparison of the results the pathological grading, severity of fECS to predict liver fibrosis.