Evaluation of Preoperative Microvascular Invasion in Hepatocellular Carcinoma Through Multidimensional Parameter Combination Modeling Based on Gd-EOB-DTPA MRI.

Background and Aims: The study established and compared the efficacy of the clinicoradiological model, radiomics model and clinicoradiological-radiomics hybrid model in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) using gadolinium ethoxybenzyl diethylene triaminepentaacetic acid (Gd-EOB-DTPA) enhanced MRI. Methods: This was a study that enrolled 602 HCC patients from two institutions. Least absolute shrinkage and selection operator (Lasso) method was used to screen for the most important clinicoradiological and radiomics features that predict MVI pre-operatively. Three machine learning algorithms were used to establish the clinicoradiological, radiomics, and clinicoradiological-radiomics hybrid models. Area under the curve (AUC) of receiver operating characteristic (ROC) curves and Delong's test were used to compare and quantify the predictive performance of the models. Results: The AUCs of the clinicoradiological model in training and validation cohorts were 0.793 and 0.701, respectively. The radiomics signature of arterial phase (AP) images alone achieved satisfying predictive efficacy for MVI, with AUCs of 0.671 and 0.643 in training and validation cohort, respectively. The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images achieved AUCs of 0.824 and 0.801 in training and validation cohorts, 0.812 and 0.805 in prospective validation and external validation cohorts, respectively. The hybrid model provided the best prediction results. The results of the Delong test revealed that there were statistically significant differences among the clinicoradiological-radiomics hybrid model, clinicoradiological model, and radiomics model (p<0.05). Conclusions: The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images based on Gd-EOB-DTPA-enhanced MRI can effectively predict MVI.

Radiomics-based classification models for HBV-related cirrhotic patients with covert hepatic encephalopathy.

INTRODUCTION: The significant abnormalities of precuneus (PC), which are associated with brain dysfunction, have been identified in cirrhotic patients with covert hepatic encephalopathy (CHE). The present study aimed to apply radiomics analysis to identify the significant radiomic features in PC and their subregions, combine with clinical risk factors, then build and evaluate the classification models for CHE diagnosis. METHODS: 106 HBV-related cirrhotic patients (54 had current CHE and 52 had non-CHE) underwent the three-dimensional T1-weighted imaging. For each participant, PC and their subregions were segmented and extracted a large number of radiomic features and then identified the features with significant discriminative power as the radiomics signature. The logistic regression analysis was employed to develop and evaluate the classification models, which are constructed using the radiomics signature and clinical risk factors. RESULTS: The classification model (R-C model) achieved best diagnostic performance, which incorporated radiomics signature (4 radiomic features from right PC), venous blood ammonia, and the Child-Pugh stage. And the area under the receiver operating characteristic curve values (AUC), sensitivity, specificity, and accuracy values were 0.926, 1.000, 0.765, and 0.848, in the testing set. Application of the radiomics nomogram in the testing set still showed a good predictive accuracy. CONCLUSIONS: This study presented the radiomic features of the right PC, as a potential image marker of CHE. The radiomics nomogram that incorporates the radiomics signature and clinical risk factors may facilitate the individualized prediction of CHE.

Aberrant brain structural network and altered topological organization in minimal hepatic encephalopathy.

PURPOSE: We aimed to investigate the multilevel impairments of brain structural network in patients with minimal hepatic encephalopathy (MHE). METHODS: Twenty-two patients with MHE and 22 well-matched healthy controls (HC) underwent structural magnetic resonance imaging (MRI) brain scans and neuropsychological evaluations. Individual brain structural networks were constructed using diffusion tensor imaging. Comparing with HC, we investigated the possible impairments of brain structural network in MHE, by applying graph-theory approaches to analyze the topological organization at global, modular, and local levels. The correlations between altered brain structural network and neuropsychological tests scores and venous ammonia levels were also examined in MHE patients. RESULTS: In the MHE group, small-worldness showed significant decrease and normalized characteristic path length showed increase at the global level. In the modular section, six modules were identified. The inter-modular connective strengths showed significant increase between modules 2 and 4 and between modules 4 and 5. The results of node analysis showed similar hub distributions in the MHE and HC groups except for the right postcentral gyrus, which was only found in the MHE group. No significant differences were found in connective strength of edges between MHE and HC groups using network-based statistics. CONCLUSION: The altered brain structural networks with reduced network integration and module segregation were demonstrated in patients with MHE. The dysconnectivity of brain structural network could provide an explanation for the brain dysfunctions of MHE.

Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study.

PURPOSE: We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). METHODS: A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. RESULTS: Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. CONCLUSION: ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE.

[Preparation of a glypican-3-targeting hepatocellular carcinoma MR probe and its molecular imaging in HepG2 cells].

OBJECTIVE: To prepare a glypican-3 (GPC3)-targeting hepatocellular carcinoma MR molecular probe and to evaluate its targeting specificity using HepG2 cells. METHODS: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation method, and the surfaces were connected with anti-GPC3 mono-antibody and paramagnetic substance Gd3+. The physical properties of the probes were investigated using fluorescence microscopy, electron microscopy, Malvern particle size analysis, inductively coupled plasma atomic emission spectroscopy (ICP-AES) and 1.5T MR imaging. The specificity of the probes to target cultured HepG2 cells was determined by laser confocal microscopy. The signal characteristics, including signal-to-noise ratio (SNR), after co-incubation with HepG2 cells were analyzed by 1.5T MR imaging. Significance of differences between multiple groups (target group, non-target group, and control group) was assessed by one-way analysis of variance, and between two groups was assessed by the LSD-t test. A difference was considered to be statistically significant at P less than 0.05. RESULTS: The GPC3-targeting hepatocellular carcinoma MR molecular probes were successfully prepared. The nanoparticles had a spherical shape, size of 495 +/- 17.5 nm, uniform size distribution, good dispersibility, no obvious aggregation, and could significantly increase the T1 signal. Using the ICP-AES measurement, 1 mol PLGA carried about 12 mol Gd3+, and as the Gd3+ concentration increased, the T1 signal increased. The prepared MR molecular probes could specifically target HepG2 cells, and could increase the T1 signal. The SNR value of the target group was 3.45 +/- 0.21, of the non-target group was 1.43 +/- 0.07, and of the control group was 1.12 +/- 0.03. The SNR value of the target group was significantly higher than that of the non-target group and the control group (P less than 0.05); there was no significant difference between the non-target group and the control group (P more than 0.05). CONCLUSION: PLGA nanoparticles, anti-GPC3 mono-antibody and paramagnetic Gd3+ can be used to successfully prepare GPC3-targeting hepatocellular carcinoma MR molecular probes which are capable of specifically targeting HepG2 cells in vitro and being detected by 1.5T MR imaging. These MR molecular probes may represent a useful noninvasive imaging method for detecting early hepatocellular carcinoma in vivo.

[Preparation and in vitro study of a high molecular weight contrast agent targeting hepatoma cells].

OBJECTIVE: To prepare a specific high molecular weight polymer contrast agent capable of specifically targeting hepatocarcinoma cells (HCC) and to investigate its affinity in vitro using HepG2 cells. METHODS: The high molecular weight polymer polylactic-co-glycolic acid (PLAG)-COOH was prepared by the double emulsion technique. PLAG-COOH microbubbles were combined with glypican-3 (GPC3) antibody to generate HCC targeting high molecular polymer ultrasound contrast agents by the carbodiimide method. The affinity for HCC cells was confirmed by measuring attachment to cultured HepG2 cells by flow cytometry and comparing the results with the properties observed for non-targeted high molecular weight polymer ultrasound contrast agents. RESULTS: The average diameter of the targeted high molecular weight polymer ultrasound contrast agents was (800+/-10) nm. In vitro targeting of HepG2 cells showed that many of the targeted high molecular weight polymer ultrasound contrast agents attached tightly to the cell surface and that the GPC3-PLGA has a particularly strong targeting ability. CONCLUSION: A HCC-specific high molecular contrast agent, GPC3-PLGA, was synthesized and evidenced a strong targeting ability towards HepG2 cells in vitro. This new agent may be exploited to improve diagnosis of liver cancer at the molecular level.

[1H magnetic resonance spectroscopy in the evaluation of high intensity focused ultrasound ablation for primary liver cancer].

To investigate the clinical value of 1H magnetic resonance spectroscopy (1H MRS) in the evaluation of high intensity focused ultrasound (HIFU) ablation for primary liver cancer. Routine magnetic resonance sequences, contrast-enhanced magnetic resonance imaging and respiratory-triggered single voxel point resolved spectroscopy sequence (PRESS) were performed on 24 patients with primary liver cancer before and after HIFU ablation. A respiratory-triggered axial T2 weighted imaging (T2WI) was used as localizer for PRESS. Spectroscopy data was transmitted to a personal computer and was post-processed with a custom software (Saker, provided by Ning Jing, an engineer in GE Healthcare). It would be considered "technical success" if the baselines of spectra were stable and main metabolites were without overlapping and could be identified. Integral areas of choline (Cho) peak at 3.2 parts per million (ppm) and lipid (Lip) peak at 1.3 ppm were measured, and the choline to lipid (Cho/Lip) ratios were calculated. The differences of areas of Cho, Lip peak and Cho/Lip ratios before and after HIFU ablation were compared by using paired samples t test, and a P value of less than 0.05 was considered statistically significant. The technical success rate of 1H-MRS was 87.50% (42/48). Integral areas of Cho peak and Lip peak of 20 patients with satisfied spectra were measured, and the Cho/Lip ratios were calculated. The Integral area of Cho peak decreased from 34 597+/-6 802 before HIFU ablation to 6 372+/-2 466 after HIFU ablation (t = 18.02, P less than 0.01). The Integral area of Lip peak increased from 147 948+/-16 317 before HIFU ablation to 149 069+/-16 345 after HIFU ablation (t = -15.11, P less than 0.01). The Cho/Lip ratio decreased from 0.23+/-0.03 before HIFU ablation to 0.04+/-0.02 after HIFU ablation (t = 25.32, P less than 0.01). 1H-MRS could provide information of metabolites changes of primary liver cancer after HIFU ablation and could be used as a complementary sequence to other magnetic resonance sequences to evaluate all around primary liver cancer after HIFU ablation.

The synthesis of a D-glucosamine contrast agent, Gd-DTPA-DG, and its application in cancer molecular imaging with MRI.

OBJECTIVE: The purpose of this study is to describe the synthesis of Gadolinium-diethylenetriamine pentaacetic acid-deoxyglucosamine (Gd-DTPA-DG) which is a d-glucosamine metabolic MR imaging contrast agent. We will also discuss its use in a pilot MRI study using a xenograft mouse model of human adenocarcinoma. METHODS: This novel contrast agent was specifically studied because of its ability to "target" metabolically active tumor tissues. In this study Gd-DTPA-DG is used to investigate how tumor tissues would react to a dose of 0.2 mmol Gd/kg over a 120 min exposure in a xenograft mouse model. These experiments used athymic mice implanted with human pulmonary adenocarcinoma (A549) as demonstrated by dynamic MRI. Alternately, another contrast agent that is not specific for targeting, Gd-DTPA, was used as the control at a similar dose of gadolinium. Efficacy of the targeted contrast agent was assessed by measuring relaxation rate in vitro and signal intensity (SI) in vivo. Statistical differences were calculated using one-way analysis of variance. RESULTS: The synthesized Gd-DTPA-DG was shown to improve the contrast of tumor tissue in this model. Gd-DTPA-DG was also shown to have a similar pharmacokinetic rate but generated a higher relaxation rate in tumor tissues relative to the control contrast Gd-DTPA. In comparison to the pre-contrast imaging, the SI of tumor tissue in the experimental group was shown to be significantly increased at 15 min after injection of Gd-DTPA-DG (p<0.001). The enhanced signal intensity spread from the edge of the tumor to the center and seemed to strengthen the idea that MRI performance would be useful in different tumor tissues. CONCLUSION: This preliminary study shows that this new chelated contrast agent, Gd-DTPA-DG, can be specifically targeted to accumulation in tumor tissue as compared to normal tissues. This targeted paramagnetic contrast agent has potential for specific cancer molecular imaging with MRI.

[CT image of liver secondary lymphoma].

OBJECTIVE: To analyze the CT image characteristics of liver secondary lymphoma. METHODS: The medical records of 13 patients were reviewed. There were 12 non-Hodgkin lymphoma cases and 1 Hodgkin lymphoma case. Abdomen CT scan was performed in all cases, plain scan and enhanced CT scan were performed in 11 cases, plain CT scan was performed in 2 cases. RESULTS: Of the 13 cases, 11 were nodular type, 1 was diffuse type, and 1 was mixed type. Plain CT scan showed low density, enhanced CT showed circular enhancement in 1 case, mild to midrange delayed enhancement in 1 case, midrange enhancement in 1 case, mild enhancement in 2 cases, blood vessel floating sign in 3 cases, no enhancement in 6 cases. CONCLUSIONS: The characteristics of liver secondary lymphoma CT image of liver secondary lymphoma includes blood vessel floating sign and enhancement.

[The application of 3D liver acquisition volume acceleration integrated with array spatial sensitivity encoding technique in liver dynamic-enhancement scanning].

OBJECTIVE: To evaluate the application of 3D liver acquisition volume acceleration (3D-LAVA) integrated with array spatial sensitivity encoding technique (ASSET) in liver dynamic-enhancement scanning. METHODS: One hundred forty-seven patients underwent conventional plain and contrast enhancement liver MR imaging. 3D-LAVA and 2D fast spoiled gradient recalled echo were used for contrast enhancement liver MR scanning in 90 and 57 patients respectively. In the 3D-LAVA group, integrated ASSET was used in 72 out of the 90 patients. Of the 57 patients who underwent examinations using 2D fast spoiled gradient recalled echo, portal vein CE-MRA was performed on 20. The ability of 3D-LAVA to detect the lesions and the advantage to shorten the acquisition time after integrating with ASSET were analyzed. Original images of 60 patients in the 3D-LAVA group were processed using MIP to illustrate the anatomy of the portal vein. They were compared with those shown by CE-MRA to evaluate the illustration abilities of the two approaches. RESULTS: 3D-LAVA is more sensitive than 2D-FSPGR in detecting metastatic hepatic carcinomas. In the 3D-LAVA group integrated with ASSET, earlier and peak arterial phase images were acquired in 34 cases; and earlier, peak and late arterial phase images were acquired in 23 cases. The illustrations of the portal vein anatomy by 3D-LAVA were similar to those shown by portal vein CE-MRA. CONCLUSION: 3D-LAVA integrated with ASSET can obtain higher quality multi-phase dynamic enhancement images of the liver in a shorter time, and in the meantime also shows the vascular anatomy.

The benefit of stretching along the artery.

Many rehabilitation exercises involve the stretching of bodies. We point out the necessity of the longitudinal stretching in arteries. The efficiency of an arterial system is closely related to the condition of the transverse vibration of the arterial walls or to the magnitudes of the area oscillation in all blood vessels. For a given blood pressure wave, a more elastic arterial wall has larger area oscillation, and therefore a higher efficiency in circulation. Elastic properties of the artery depend on the longitudinal stretching. In vitro experiment on pig aorta confirms that proper longitudinal stretching increases its elasticity and benefits to the circulatory system.

The eccentric position of the heart in the mammalian body and optimal energy transfer in single tube models.

Many phenomena cannot be explained by traditional haemodynamics models. For example, the hearts of all mammals are neither at one end of the circulatory system nor at the geometric centre. Based on a new circulation model, we report that if the heart is located at either of these two positions, the energy saving rule will be violated. We assume that the main arterial system is under a steady, distributed transverse vibration with the heart as the input power source. The equation of motion of the artery is governed by a new pressure wave equation with total energy. We analyse the effects of the heart position on the pressure pulse shape and the spectrum. By a simplifying T-tube model, we find that there are many harmonic oscillating modes for the overall arterial system. The position of the heart affects the weights of different modes. If the heart is at the midpoint or at one end of the body, none of the even harmonic modes can be excited. If the heart is at a third along the whole system, the third oscillation mode in the system is missing. Thus, from an efficiency point of view, this model gives a strong reason for all mammals' hearts being at an eccentric position. Tube simulations were carried out to confirm the theoretical prediction. A new standing wave model to analyse the variation of the pressure pulse shape along the artery is discussed. The interesting result indicates that our new pressure wave equation possesses a high problem solving potential. It provides a new tool for studying arterial dynamics.