Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

BACKGROUND:Hepatocellular carcinoma(HCC)is a common malignant tumor in China,and early diagnosis is critical for patient outcome.In patients with HCC,it is mostly based on liver cirrhosis,developing from benign regenerative nodules and dysplastic nodules to HCC lesions,and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection.Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion,blood volume and permeability.These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion(CTP)imaging and can be used to assess the growth of HCC.This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. METHODS:CTP was performed in 30 volunteers without liver disease(control subjects)and 49 patients with liver disease (experimental subjects:27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre-and post-contrast triple-phase CT and CTP study.A mathematical deconvolution model was applied to provide hepatic blood flow(HBF),hepatic blood volume(HBV), mean transit time(MTT),permeability of capillary vessel surface(PS),hepatic arterial index(HAI),hepatic arterial perfusion(HAP)and hepatic portal perfusion(HPP)data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC.RESULTS:In normal liver,the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC.The value of HBF at the tumor rim was significantly higher than that in the controls.HBF,HBV,HAI,HAP and HPP,but not MTT and PS,were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CONCLUSIONS:CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

Early changes of hepatic hemodynamics measured by functional CT perfusion in a rabbit model of liver tumor

BACKGROUND:Early detection and treatment of hepatocellular carcinoma is crucial to improving the patients’ survival.The hemodynamic changes caused by tumors can be serially measured using CT perfusion.In this study,we used a CT perfusion technique to demonstrate the changes of hepatic hemodynamics in early tumor growth,as a proof-of-concept study for human early hepatocellular carcinoma.METHODS:VX2 tumors were implanted in the liver of ten New Zealand rabbits.CT perfusion scans were made 1 week(early) and 2 weeks(late) after tumor implantation.Ten normal rabbits served as controls.CT perfusion parameters were obtained at the tumor rim,normal tissue surrounding the tumor,and control liver;the parameters were hepatic blood flow,hepatic blood volume,mean transit time,permeability of capillary vessel surface,hepatic arterial index,hepatic arterial perfusion and hepatic portal perfusion.Microvessel density and vascular endothelial growth factor were correlated.RESULTS:At the tumor rim,compared to the controls,hepatic blood flow,hepatic blood volume,permeability of capillary vessel surface,hepatic arterial index,and hepatic arterial perfusion increased,while mean transit time and hepatic portal perfusion decreased on both early and late scans(P<0.05).Hepatic arterial index increased(135%,P<0.05),combined with a sharp increase in hepatic arterial perfusion(182%,P<0.05) and a marked decrease in hepatic portal perfusion(-76%,P<0.05) at 2 weeks rather than at 1 week(P<0.05).Microvessel density and vascular endothelial growth factor showed significant linear correlations with hepatic blood flow,permeability of capillary vessel surface and hepatic arterial index,but not with hepatic blood volume or mean transit time.CONCLUSION:The CT perfusion technique demonstrated early changes of hepatic hemodynamics in this tumor model as proof-of-concept for early hepatocellular carcinoma detection in humans.

EVALUATION OF CIRRHOTIC LIVER WITH PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING:A PRELIMINARY EXPERIMENTAL STUDY IN ANIMAL MODELS WITH HALF-LIVER CIRRHOSIS

Objective To investigate the role of peffusion-weighted magnetic resonance imaging （MRI） in evaluation of cirrhotic fiver. Methods With a 4F catheter, 1% diluted carbon tetrachloride （ 1 ml/kg） was selectively injected into fight or left hepatic artery of 12 dogs fortnightly. The half fiver into which carbon tetrachloride was injected was called as study side （SS）, while the other half fiver without carbon tetrachloride injection was called as study control side （SCS）. Conventional and peffusion-weighted MRI were performed in every 4 weeks. Via a 4F catheter, 5ml gadolinium diethylentriamine pentaaceti acid （Gd-DTPA） dilution was injected into superior mesenteric artery at the 5th scan. The signal intensity-thne curves of SS, SCS, and portal vein were completed in MR workstation. The maximal relative signal increase （ MRSI）, peak time （ tp）, and slope of the curves were measured. Results On conventional MR images, no abnormalities of externality and signal intensity were observed in both SS and SCS of fiver at each stage. The mean tp, MP, SI, and slope of intensity-time curves in normal fiver were 10. 56 seconds, 1.01, and 10. 23 arbitrary unit （au）/s, respectively. Three parameters of curves didn＇t show obvious change in SCS of fiver at every stage. Abnormal perfusion curves occurred in SS of fiver at the 12th week after the 1st injection. The abnormality of perfusion curve in SS was more and more serious as the times of injection increased. The mean tp, IVlRSI, and slope intensity-time curves in SS of fiver were 19.45 seconds, 0. 43, and 3. 60 au/s respectively at the 24th week. Conclusion Perfusion-weighted imaging can potentially provide information about portal peffusion of hepatic parenchyma, and to some degree, reflect the severity of cirrhosis.

Detection and differentiation of early hepatocellular carcinoma from cirrhosis using CT perfusion in a rat liver model

BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.

Perfusion CT findings in liver of patients with tumor during chemotherapy

AIM: To investigate the microcirculation changes in liver of patients with tumor during chemotherapy by perfusion computed tomography (CT). METHODS: Sixty patients with tumor and 20 controls were enrolled in this study. Perfusion CT parameters of patients and controls were compared, including hepatic perfusion index (HPI), mean transit time (MTT), and permeability-surface area product (PS). Correlation between perfusion CT parameters, treatment cycle and alanine aminotransferase (ALT) level was studied. RESULTS: No difference was found in HPI (25.68% ± 7.38% vs 26.82% ± 5.13%), MTT (19.67 ± 5.68 s vs21.70 ± 5.43 s) and PS (17.00 ± 4.56 mL/100 mL per min vs 19.92 ± 6.35 mL/100 mL per min) between pa- tients and controls. The HPI and MTT were significantly higher in patients undergoing 2 cycles of chemotherapy than in controls and those undergoing 1 cycle of che- motherapy (29.76% ± 5.87% vs 25.68% ± 7.38% and 25.35% ± 4.05%, and 25.61 ± 5.01 s vs 19.67 ± 5.68 s and 19.74 ± 4.54 s, respectively, P < 0.05). The HPI was higher in patients with hepatic steatosis than in controls and those without hepatic steatosis (30.85% ± 6.17% vs 25.68% ± 7.38% and 25.70% ± 4.24%, P < 0.05). Treatment cycle was well correlated with HPI and MTT (r = 0.40, r = 0.50, P < 0.01). ALT level was not correlated with perfusion CT parameters. CONCLUSION: HPI and MTT are significantly increased in patients with tumor during chemotherapy and well correlated with treatment cycle. Chemotherapy affects hepatic microcirculation in patients with tumor. Changes in hepatic microcirculation can be quantitatively assessed by perfusion CT.

Three-dimensional-arterial spin labeling perfusion correlation with diabetes-associated cognitive dysfunction and vascular endothelial growth factor in type 2 diabetes mellitus rat

BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.

Experimental Study of Multi-slice Spiral CT Perfusion Imaging in VX_ 2 Soft-tissue Tumor of Rabbits

An experimental animal model of malignant soft-tissue tumor was established to investigate the applied value of multi-slice spiral CT perfusion imaging preliminarily. Ten New Zealand white rabbits which were implanted with VX2 tumor in either proximal thigh were subjected to CT plain scan and perfusion scan two weeks later respectively, then the original perfusion images were transmitted to AW4.0 Workstation. The functional maps and perfusion parameters including blood flow （BF）, blood volume （BV）, mean transit time （MTT） and permeability surface （PS） were computed and analyzed. All the values of BF, BV and PS in VX2 soft-tissue tumors were obviously higher while the MTT-values were lower than those in the normal muscular tissues significantly. It was suggested that multi-slice spiral CT perfusion imaging is an accurate, convenient and relatively safe functional imaging technique, and can give a quantitative assessment to angiogenesis and blood perfusion of soft-tissue tumors.

Value of MR perfusion imaging after intervention treatment of hepatic cancer

Objective： To investigate the value of MR perfusion imaging in evaluating the curative effect of intervention treatment of hepatic cancer. Methods： 36 patients underwent MR perfusion imaging after intervention treatment. The quantization results were differed between carcinoma residue and benign tissue. And the diagnosis accuracy was judged, Results： There was a significant difference in mean MSI between residue tumor after surgery and the benign enhancement area. The timeintension curve of residue tumor was observed to ascend rapidly to reach the peak, whereas that of the enhancement tissue ascended slowly to reach the peak. The sensitivity and specificity of PWl on detection of residuary or recurrent tumor were 0.89 and 0.73 respectively. Conclusion： PWl is a very sensitive imaging technique that can be used to distinguish liver tissue condition after surgery. PWI contributed to early stage diagnosis and dynamic monitoring following HCC surgery.

A correlation of computed tomography perfusion and histopathology in tumor edges of hepatocellular carcinoma

BACKGROUND： The peripheral morphologic characteristics of hepatocellular carcinoma （HCC） reflect tumor growth patterns. Computed tomography （CT） perfusion is a new method to analyze hemodynamic changes in tissues. We assessed the relationship between CT perfusion and histopathologic findings in the periphery of HCC lesions. METHODS： Non-contrast CT, enhanced dual-phase CT, and CT perfusion were performed on 77 subjects （47 patients and 30 controls）. Based on the imaging findings of enhanced dual- phase CT, the tumor edges were classified into three types： type Ⅰ （sharp）; type Ⅱ （blurry）; and type Ⅲ （mixed）. The CT perfusion parameters included hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. The tissue sections from resected specimens were subjected to routine hematoxylin and eosin staining and immunohistochemical staining for CD34. The correlations between microvessel density （MVD） and the CT perfusion parameters were analyzed using Pearson＇s product-moment correlation coefficient. Changes in the perfusion parameters in tumor edges of different tumor types were evaluated. RESULTS： Type Ⅰ （sharp）： the pathologic findings showed fibrous connective tissue capsules in the tumor edges, and an MVD 〈30/ram2. Type Ⅱ （blurry）： the histology showed that the edges were clear with no capsules and an MVD 〉30/ram2. Type Ⅲ （mixed）： the pathology was similar to that of types I and II, and an MVD 〉30/mm~. Hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion were significantly increased in the tumor edges of HCC patients compared to those of the controls （P〈0.05）. The correlation between CT perfusion parameters and MVD was higher in blurry tumor edges of type II than in those of types Ⅰ or Ⅲ. CONCLUSION： CT perfusion imaging of tumor edges may be helpful in revealing histopathological features, and indirectly reflect angiogenic changes of HCCs.

A Controlled Study on Comparing Differences in CT Perfusion Imaging between Rabbits inoculated with VX2 Lung Tumor and Patients with Squamous Cell Carcinoma of the Lung

OBJECTIVE By analysis and evaluation of the perfusion images and perfusion parameters of the rabbits with VX2 lung tumor, the association between the perfusion parameters and tumor angiogenesis of patients with squamous cell carcinoma of the lung has been studied in order to establish a non-invasive and effective way to detect tumor blood supply, which is be able to exhibit hemodynamic data in tumors during cancer treatments. METHODS Fifteen Netherlands rabbits inoculated with VX2 lung tumor （rabbit group） and 25 patients with squamous cell carcinoma of the lung （patient group） received a multi-slice spiral CT perfusion imaging test using the Netherlands PHILIPS Brilliance 16-slice spiral CT and a U.S. MEDRAD binocular highpressure syringe. Image postprocessing was done using the special perfusion software and EBW 4.0 Workstation. Perfusion volume （PV）, peak enhanced increment （PEI）, transit time peak （TTP）, and blood volume （BV） were measured and analyzed. RESULTS In the rabbit group, the values of the PV, PEI, TTP, and BV of the tumor margin were （53.89 ± 13.38） mL/（min.mL）, （45.71 ± 15.52） Hu, （39.29 ± 10.10） sec, and （31.45 ± 18.19） mL/100 g, respectively; these values of the tumor center were （36.57 ± 14.17） mL/（min.mL）, （28.64 ± 11.74） Hu, （39.00 ＋ 9.78） sec, and （19.76 ± 13.95） mL/100 g, respectively; the values of the muscles were （12.45± 4.38） mL/（min.mL）, （10.98 ± 5.03） Hu, （38.86 ± 10.04） sec, and （5.38 ±2.87） mL/100 g, respectively. The values of the relative perfusion volume （RPV）, relative peak enhanced increment （RPEI）, and relative blood volume （RBV） of the tumor margin were 4.38 ± 1.45, 3.96± 1.45, 9.99 ± 11.7, respectively; these values of the tumor center were 2.14 ± 1.08, 1.83±1.45, 4.17 ±3.39, respectively. The values of the PV, PEL BV of the tumor margin vs. the values of the muscles developed t-values, which were 15.028, 10.79, and 5.88, respectively （P ≤ 0.01）, with statistical significance; the values of the PV, PEI, BV of the tumor center vs. the values of the muscles produced t-values, which were 8.67, 7.49, and 4.55, respectively （P 〈 0.01）, with statistical significance. The values of the TTP of the tumor margin vs. TTP values of the muscles, and the TTP values of the tumor center vs. TTP values of the muscles developed t-values, which were 1.7 and 0.806, respectively （P ≥ 0.05）, without statistical significance. In the patient group, the values of the PV, PE, TTP, and BV of the tumor margin were （88.95 ± 30.89） mL/（min.mL）, （61.87 ± 27.31） Hu, （37.72 ± 12.53） sec, and （18.38 ± 7.2） mL/100 g, respectively; these values of the tumor center were （39.77 ± 18.29） mL/（min.mL）, （14.57 ± 8.1） Hu, （35.64 ± 12.41） sec, and （11.22 ± 6.02） mL/100 g, respectively; these values of the muscles were （12.45 ± 6.5） mL/（min.mL）, （6.14 ± 2.66） Hu, （35.68± 12.35） sec, and （2.23 ± 1.11） mL/100 g, respectively. The values of the RPV, RPEI, and RBV of the tumor margin were 8.05 ± 5.04, 8.87 ± 4.32, and 12.16 ± 8.49, respectively; these values of the tumor center were 2.39 ± 1.68, 2.97 ± 2.1, 3.53 ± 2.82, respectively. The values of the PV, PEI, BV of the tumor margin in the patient group vs. the values of the muscles produced t-values, which were 13.8, 10.85, and 12.22, respectively （P 〈 0.01）, with significant differences; these values of the tumor center vs. the values of the muscles developed t-values, which were 9.158, 6.26, 8.654, respectively （P 〈 0.01）, with significant differences. The TTP value of the tumor margin vs. that of the muscles produced t-value, which was 0.371, and the TTP value of the tumor center vs. that of the muscles developed t-value, which was 1 （P 〉 0.05）, without statistical difference. CONCLUSION CT perfusion imaging technics demonstrates directly dynamic changes of blood flow to tumors, which assists in identifying tumor growth and necrosis, therefore, this research provides an evidence-based guidelines for the treatment of human lung squamous cell carcinoma and has far-reaching clinical significance.

Dynamic Contrast-Enhanced Perfusion MR Imaging Measurements of Endothelial Permeability: Differentiation between Atypical and Typical Meningiomas

BACKGROUND: AND PURPOSE: The measurement of relative cerebral blood volume (rCBV) and the volume transfer constant (K(trans)) by means of dynamic contrast-enhanced (DCE) perfusion MR imaging (pMRI) can be useful in characterizing brain tumors. The purpose of our study was to evaluate the utility of these measurements in differentiating typical meningiomas and atypical meningiomas. METHODS: Fifteen patients with pathologically confirmed typical meningiomas and seven with atypical meningiomas underwent conventional imaging and DCE pMRI before resection.rCBV measurements were calculated by using standard intravascular

Detection of liver micrometastases from colorectal origin by perfusion CT in a rat model

BACKGROUND: Some patients with colorectal carcinoma have liver metastases(LMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography(CT).METHODS: LMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic(day 10), interval(day 17), and macroscopic stage(day 34). Perfusion parameters were computed using a dualinput one-compartmental model.RESULTS: Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, LMs at interval(1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42%(P=0.004) and 41%(P=0.029) in hepatic transit time and an increase of 292%(P=0.073) and 240%(P=0.001) in portal delay, respectively.CONCLUSIONS: LMs with a mean diameter between 1.1 and2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection.

Dynamic Changes of the CT Perfusion Parameters in the Embolic Model of Cerebral Ischemia

Summary: To study the dynamic changes of CT perfusion parameters during the first 12 h in the embolic cerebral ischemia models. Local cerebral ischemia model were established in 7 New Zealand white rabbits. All CT scans were performed with a GE Lightspeed 16 multislice CT. Following the baseline scan, further CT perfusion scans were performed at the same locations 20 min, 1-6 h and 8, 10 and 12 h after the embolus delivery. Maps of all parameters were obtained by CT perfusion software at each time point. The brains, taken 12 h after the scan, were sliced corresponding to the positions of the CT slices and stained by 2,3,5-triphenyltetrazolium chloride (TTC). On the basis of the TTC results, the ischemic sides were divided into 3 regions: core, penumbra and the relatively normal region. The changes of all parameters were then divided into 3 stages. In the first two hours (the first stage), the CBV dropped more remarkably in the core than in the penumbra but rose slightly in the relatively normal region while the CBF decreased and MTT, TTP extended in all regions to varying degrees. In the 2nd-5th h (the second stage), all the parameters fluctuated slightly around a certain level. In the 5th-12th h (the third stage), the CBV and CBF dropped, and MTT and TTP were prolonged or shortened slightly in the core and penumbra though much notably in the former while the CBV, CBF rose and MTT, TTP were shortened remarkably in the relatively normal region. We experimentally demonstrated that the location and extent of cerebral ischemia could be accurately assessed by CT perfusion imaging. The pathophysiology of the ischemia could be reflected by the CT perfusion to varying degrees.

Experimental system for perfusion imaging and time-intensity processing based on ultrasound contrast agent

Objective： To present a self-developed experimental system for basic studies of blood perfusion imaging and time-intensity evaluating based on ultrasound contrast agent. Methods ： The experimental system performed the image reconstruction and time-intensity processing with radio frequency signals. The system was comprised of ultra-high speed hardware data acquisition interface and low computational cost algorithms. The self-made contrast agent ,blood mimic phantom and capillary phantom model were used to validate the experimental system. Results： The images acquired in blood phantoms with linear-array and curve-array transducers were given. The time-intensity curves corresponding to selected region of interestsequence were demonstrated. It was also shown the time-intensity based decay curves and a decay of ultrasound contrast agent under different ultrasound powers. Conclusion： Several suited from two in vitro phantom models show that the experimental system can be used to f blood perfusion and further clinical studies of microvasculature perfusion.

Dynamic contrast-enhanced magnetic resonance perfusion weighted imaging in astrocytomas: correlation with histopathology and immunohistochemistry

Objective:To investigate magnetic resonance perfusion weighted imaging and its relationship with the grading and the expression of vascular endothelial growth factor (VEGF) and angiogenesis in astrocytomas. Methods: A collection of 34 patients with astrocytomas proved by surgery and pathology were examined by magnetic resonance imaging(MRI), with 26 cases of gradeⅠ-Ⅱ(low-grade) and 8 cases of grade Ⅲ-Ⅳ(high-grade). MR perfusion images were obtained with spin-echo echo planar imaging (SE-EPI) techniques. Expression of VEGF was examined by immunohistochemical method of streptavidin-biotin-peroxidase(SP). The vascular development was measured by micro-vascular density (MVD) which was immunostained with anti-factor Ⅷ-related antigen monoclonal antibody. Results: Both of the expression of VEGF and the angiogenesis in 34 cases of astrocytomas were significantly correlated to the maximum relative cerebral blood volume (Max rCBV) (r=0.604, P<0.001;r=0.625, P<0.001, respectively). The Max rCBV and the expression of VEGF, MVD in high-grade astrocytomas were significantly higher than that of in low-grade astrocytomas (t= 3.0, P=0.017; t=7.08, P=0.01;t=3.37,P=(0.011,) respectively). Conclusion: MR perfusion weighted imaging might be a valuable method in in vivo study of the angiogenesis of astrocytomas and evaluating their malignant degree and prognosis.

Contrast investigation of multi-slice spiral CT perfusion imaging and pathological findings in VX2 soft-tissue tumor of rabbits

Objective: To perform a contrast investigation of multi-slice spiral CT (MSCT) perfusion imaging and pathological findings in VX2 soft-tissue tumor of rabbits, and discuss the applicative value of multi-slice spiral CT perfusion imaging in soft-tissue tumors. Methods: 8 Newzealand white rabbits were implanted with 0.1 ml VX2 tumor tissue suspension in bilateral proximal thighs. 14 days and 21 days later, CT plain scan and perfusion scan were performed on these rabbits respectively, then the images were transmitted to AW4.0 workstation, the functional maps and perfusion parameters including blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS) were computed and analyzed. Subsequently, the rabbits were sacrificed, the tumors of which were taken out for pathological examination. The correlation between MSCT functional parametric images and pathological findings was analyzed. Results: All the values of BF, BV and PS of VX2 soft-tissue tumors were obviously higher while the MTT-values were lower than those of the normal muscular tissues significantly (P<0.001). Conclusion: Multi-slice spiral CT perfusion imaging is an accurate, convenient and relatively safe functional imaging technique, which can give a quantitative assessment to blood perfusion and angiogenesis of soft-tissue tumors.

Advances in arterial spin labeled cerebral perfusion imaging in cerebrovascular diseases

Cerebrovascular disease is a disease with high morbidity,disability and mortality rates,which seri-ously affects the daily life of patients and is a heavy burden on families and society.Arterial spin labeling(ASL)is a magnetic resonance imaging(MRI)technology that uses the magnetic labeling of hydrogen atoms in arterial blood as tracers to noninvasively evaluate brain blood flow.ASL does not require injection of an exogenous contrast agent,and has the advantages of no radiation,simplicity and low cost.In cerebrovascular diseases,ASL can evaluate the collateral cerebrovascular circulation and abnormal perfusion of brain tissue,which can provide a reliable basis for early diagnosis and clinical decision-making.This study reviewed ASL and its application in the diagnosis,treatment and prognosis of cerebrovascular diseases.

A Correlative Study between CT Perfusion Parameters and Angiogenesis in Rabbit VX2 Liver Tumors

Objective: The purpose of this study was to evaluate the correlation between CT perfusion parameters and the hypoxia-inducible factor-1 alpha (HIF-1α), vascular en-dothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and microvessel density (MVD) marked by CD34 molecular of rabbit VX2 liver tumors and to investigate the value of CT perfusion imaging in evaluating tumor angiogenesis. Material and methods: Twenty-four cases of rabbit VX2 liver tumor were performed by CT perfusion scanning. Hepatic artery perfusion (HAP), portal vein perfusion (PVP), total hepatic blood flow (THBF) and hepatic perfusion index (HPI) were measured by perfusion software. HIF-1α, VEGF and MMP-2 expression and MVD were detected in the 24 rabbit VX2 liver tumor tissue samples using immunohistochemical method. The correlation between the HIF-1α, VEGF, MMP-2 expression and MVD and CT perfusion parameters were analyzed. Results: Correlation analysis revealed that the expression of HIF-1α, MMP-2, MVD were positively related to the HAP, THBF, HPI (p < 0.01), but no relations with PVP (p > 0.05);and correlation analysis revealed that the expression of VEGF was positively related to the HAP, HPI (p 0.05). There was a positive relationship between the expression of HIF-1α, VEGF, MMP-2 and MVD (p < 0.01). Conclusions: CT perfusion imaging can reflect the blood perfusion of the rabbit VX2 liver tumors and evaluate the information of angiogenesis about tumors.

Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

BACKGROUND Liver transplant(LT)patients have become older and sicker.The rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT mortality.Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center.We developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning model.We addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each case.The modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac assessments.Model performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature impacts.The dataset was split into training(75%)and testing(25%)sets.Calibration was evaluated using the Brier score.We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting.Scikit-learn and SHAP in Python 3 were used for all analyses.The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTS Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 years.The majority,66.1%,were male.The XGBoost model achieved an impressive AUROC of 0.89 during the training stage.This model exhibited accuracy,precision,recall,and F1-score values of 0.84,0.85,0.80,and 0.79,respectively.Calibration,as assessed by the Brier score,indicated excellent model calibration with a score of 0.07.Furthermore,SHAP values highlighted the significance of certain variables in predicting postoperative MACE,with negative noninvasive cardiac stress testing,use of nonselective beta-blockers,direct bilirubin levels,blood type O,and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level.These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE,making it a valuable tool for clinical practice.CONCLUSION Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE,using both cardiovascular and hepatic variables.The model demonstrated impressive performance,aligning with literature findings,and exhibited excellent calibration.Notably,our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data,reinforcing the model’s value as a reliable tool for predicting post-LT MACE in clinical practice.

Use of various CT imaging methods for diagnosis of acute ischemic cerebrovascular disease

Thirty-four patients with cerebral infarction and 18 patients with transient ischemic attack were examined by multi-slice spiral CT scan, CT perfusion imaging, and CT angiography within 6 hours after onset. By CT perfusion imaging, 29 cases in the cerebral infarction group and 10 cases in the transient ischemic attack group presented with abnormal blood flow perfusion, which corresponded to the clinical symptoms. By CT angiography, various degrees of vascular stenosis could be detected in 41 patients, including 33 in the cerebral infarction group and eight in the transient ischemic attack group. The incidence of intracranial artery stenosis was higher than that of extracranial artery stenosis. The intracranial artery stenosis was located predominantly in the middle cerebral artery and carotid artery siphon, while the extracranial artery stenosis occurred mainly in the bifurcation of the common carotid artery and the opening of the vertebral artery. There were 34 cases （83%） with convict vascular stenosis and perfusion abnormalities, and five cases （45%） with perfusion abnormalities but without convict vascular stenosis. The incidence of cerebral infarction in patients with National Institutes of Health Stroke Scale scores 〉 5 points during onset was significantly higher than that in patients with National Institutes of Health Stroke Scale scores 〈 5 points. These experimental findings indicate that the combined application of various CT imaging methods allows early diagnosis of acute ischemic cerebrovascular disease, which can comprehensively analyze the pathogenesis and severity of acute ischemic cerebrovascular disease at the morphological and functional levels.