Advances in application of novel magnetic resonance imaging technologies in liver disease diagnosis

Liver disease is a major health concern globally,with high morbidity and mortality rates.Precise diagnosis and assessment are vital for guiding treatment approaches,predicting outcomes,and improving patient prognosis.Magnetic resonance imaging(MRI)is a non-invasive diagnostic technique that has been widely used for detecting liver disease.Recent advancements in MRI technology,such as diffusion weighted imaging,intravoxel incoherent motion,magnetic resonance elastography,chemical exchange saturation transfer,magnetic resonance spectroscopy,hyperpolarized MR,contrast-enhanced MRI,and radiomics,have significantly improved the accuracy and effectiveness of liver disease diagnosis.This review aims to discuss the progress in new MRI technologies for liver diagnosis.By summarizing current research findings,we aim to provide a comprehensive reference for researchers and clinicians to optimize the use of MRI in liver disease diagnosis and improve patient prognosis.

Characteristics and pathological mechanism on magnetic resonance diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

AIM: To investigate dynamic characteristics and pathological mechanism of signal in rabbit VX-2 tumor model on diffusion-weighted imaging (DWI) after chemoembolization. METHODS: Forty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity opened. Forty VX-2 tumor models from them were divided into four groups. DWI was performed periodically and respectively for each group after chemoembolization. All VX-2 tumor samples of each group were studied by pathology. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance between different time groups, different area groups or different b-value groups was calculated by using SPSS12.0 software. RESULTS: Under b-value of 100 s/mm2, ADC values were lowest at 16 h after chemoembolization in area of VX-2 tumor periphery, central, and normal liver parenchyma around tumor, but turned to increase with further elongation of chemoembolization treatment. The distinction of ADC between different time groups was significant respectively (F = 7.325, P < 0.001; F = 2.496, P < 0.048; F = 6.856, P < 0.001). Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor, increased quickly in sixteen h after chemoembolization but, from the 16th h to the 48th h, cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at, and then increased continually. After chemoembolization, Cellular necrosis in the area of VX-2 tumor periphery was more significantly high than that before chemoembolization. The areas of dead cells in VX-2 tumors manifested low signal and high ADC value, while the areas of viable cells manifested high signal and low ADC value. CONCLUSION: DWI is able to detect and differentiate tumor necrotic areas from viable cellular areas before and after chemoembolization. ADC of normal liver parenchyma and VX-2 tumor are influenced by intracellular edema, tissue cellular death and microcirculation disturbance after chemoembolization.

Characteristics of liver on magnetic resonance diffusion-weighted imaging:Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

AIM： To investigate dynamical and image pathological characteristics of the liver on magnetic resonance （MR） diffusion-weighted imaging （DWI） in the rabbit VX-2 tumor model. METHODS： Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging （MRI） were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically. RESULTS： The rate of lump detected by DWI, TlWI and T2WI was 78.7%, 10.7% and 53.5% （X^2 =32.61, P 〈 0.001） on the 7th d after implantation and 95.8%, 54.3% and 82.9% （X^2 = 21.50, P 〈 0.001） on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal diffusion coefficient （ADC）. did not decrease on the 7th on the map of apparent The signal of VX tumors d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually distinct and internal signals of tumor became progressively uneven. CONCLUSION： The manifestations of viable, necrotic and liquefied or cystic areas in VX-2 tumors on DWI are typical and DWI is of significant and potential values in clinical application in both the early detection and diagnosis of liver tumors.

Diagnostic value of gadobenate dimeglumine-enhanced hepatocyte-phase magnetic resonance imaging in evaluating hepatic fibrosis and hepatitis

AIM To evaluate the diagnostic value of gadobenate dimeglumine(Gd-BOPTA)-enhanced hepatocyte-phase magnetic resonance imaging(MRI) in evaluating hepatic fibrosis and hepatitis.METHODS Hepatocyte-phase images of Gd-BOPTA-enhanced MRI were retrospectively evaluated in 76 patients with chronic liver disease. These patients were classified into five groups according to either the histopathological fibrosis stage(S0-S4) or the histopathological hepatitis grade(G0-G4). The relative enhancement ratio(RE) of the liver parenchyma in the T1-vibe sequence was calculated by measuring the signal intensity before(SI pre) and 90 min after(SI post) intravenous injection of Gd-BOPTA using the following formula: RE =(SI post-SI pre)/SI pre. One-way analysis of variance was used to compare the difference between the relative RE in the hepatocyte phase(REh) and the stage of hepatic fibrosis and the grade of hepatitis. Pearson's productmoment correlation analysis was used to evaluate the relationship between the REh and the levels of serologic liver functional parameters.RESULTS According to histopathological hepatic fibrosis stage, the 76 patients were classified into five groups: 16 in S0, 15 in S1, 21 in S2, 9 in S3, and 15 in S4 group. According to histopathological hepatitis grade, the 76 patients were also classified into five groups: 0 in G0, 44 in G1, 22 in G2, 8 in G3, and 2 in G3 group. With regard to the stage of hepatic fibrosis, REh showed significant differences between the S2 and S3 groups and between the S2 and S4 groups(P < 0.05), but no significant difference was observed between the other groups. With regard to the grade of hepatitis, REh showed significant differences between the G1 and G2 groups and between the G1 and G4 groups(P < 0.05), but no significant difference was observed between the other groups. Increased REh showed correlations with decreased serum levels of TB, ALT and AST(P < 0.05). CONCLUSION To some extent, measuring the REh using Gd-BOPTAenhanced MRI might be a noninvasive technique for assessing the stage of hepatic fibrosis. This method is able to differentiate no/mild hepatitis from advanced hepatitis. TB, ALT and AST levels can predict the degree of liver enhancement in the hepatocyte phase of Gd-BOPTA-enhanced MRI.

Pathological and MR-DWI study of the acute hepatic injury model after stem cell transplantation

AIM： To investigate apparent diffusion coefficient （ADC） values as an indication of reconditioning of acute hepatic injury （AHI） after allogeneic mononuclear bone marrow cell （MBMC） transplantation. METHODS： Three groups were used in our study： a cell transplantation group （n = 21）, transplantation control group （n = 21） and normal control group （n = 10）. AHI model rabbits in the cell transplantation group were injected with 5 mL of MBMC suspension at multiple sites in the liver and the transplantation controls were injected with 5 mL D-Hanks solution. At the end of the 1st, 2nd and 4th wk, 7 rabbits were randomly selected from the cell transplantation group and trans- plantation control group for magnetic resonance diffu- sion-weighted imaging （MR-DWI） and measurement of the mean ADC values of injured livers. After MR-DWI examination, the rabbits were sacrificed and the livers subjected to pathological examination. Ten healthy rab- bits from the normal control group were used for MR- DWI examination and measurement of the mean ADC value of normal liver. RESULTS： At all time points, the liver pathological scores from the cell transplantation group were significantly lower than those in the transplantation control group （27.14± 1.46 vs 69.29± 6.16, 22.29 ± 2.29 vs 57.00± 1.53, 19.00 ± 2.31 vs 51.86 ± 6.04, P = 0.000）. The mean ADC values of the cell transplantation group were significantly higher than the transplantation con- trol group （（1.07± 0.07） ×10^-3 mm2/s vs （0.69 ± 0.05） ×10^-3 mm2/s, （1.41± 0.04） ×10^-3 mm2/s vs （0.84± 0.03） ×10^-3 mm2/s, （1.68 ± 0.04） ×10^-3 mm2/s vs （0.86± 0.04） ×10^-3 mm2/s, P = 0.000）. The pathological scores of the cell transplantation group and transplantation control group gradually decreased. However, their mean ADC values gradually increased to near that of the normal control. At the end of the 1st wk, the mean ADC values of the cell transplantation group and transplantation control group were significantly lower than those of the normal control group [（1.07 ± 0.07） ×10^-3 mm2/s vs （± 0.03） ×10^-3 mm2/s, （0.69± 0.05） ×10^-3 mm2/s vs （1.76 ± 0.03） ×10^-3 mm2/s, P = 0.000]. At any 2 time points, the pathological scores and the mean ADC values of the cell transplantation group were significantly different （P = 0.000）. At the end of the 1st wk, the pathological scores and the mean ADC values of the transplantation control group were significantly different from those at the end of the 2nd and 4th wk （P = 0.000）. However, there was no significant difference between the 2nd and 4th wk （P = 0.073 and 0.473, respectively）. The coefficient of correlation between the pathological score and the mean ADC value in the cell transplantation group was -0.883 （P = 0.000） and -0.762 （P = 0.000） in the transplantation control group. CONCLUSION： Tracking the longitudinally dynamic change in the mean ADC value of the AHI liver may reflect hepatic injury reconditioning after allogeneic MBMC transplantation.

Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

AIM: To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and Strept Avidin-Biotin Complex (SABC) immunohistochemical staining. RESULTS: The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P < 0.001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P < 0.001). PCNAand nm23 expression in the VX-2 tumor periphery first increased and then decreased (P < 0.001 and P = 0.03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm2, there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P < 0.001), and PCNA expression in VX-2 tumor periphery influenced the ADC. CONCLUSION: The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.

Effect of preoperative transcatheter arterial chemoembolization on proliferation of hepatocellular carcinoma cells

AIM： To evaluate the effect of preoperative transcatheter arterial chemoembolization （TACE） on proliferation of hepatocellular carcinoma （HCC） cells. METHODS： A total of 136 patients with HCC underwent liver resection. Of 136 patients, 79 patients received 1 to 5 courses of TACE prior to liver resection （TACE group）, who were further subdivided into four groups： Group A （n = 11） who received i to 4 courses of chemotherapy alone; Group B （n = 33） who received i to 5 courses of chemotherapy combined with iodized oil; Group C （n = 23） who received i to 3 courses of chemotherapy combined with iodized oil and gelatin sponge; and Group D （n = 12） who received 1 to 3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge. The other 57 patients only received liver resection （non- TACE group）. The expressions of Ki-67 and proliferating cell nuclear antigen （PCNA） protein were detected in the liver cancer tissues by immunohistochemical method. RESULTS： The Ki-67 protein expression was significantly lower in Groups C and D as compared with non-TACE group （31.35% ± 10.85% vs 44.43% ± 20.70%, 30.93% ± 18.10% vs 44.43% ± 20.70%, respectively, P 〈 0.05）. The PCNA protein expression was significantly lower in Groups C and D as compared with non-TACE group （49.61% ± 15.11% vs 62.92% ± 17.21%, 41.16% ± 11.83% vs 62.92% ± 17.21%, respectively, P 〈 0.05）. The Ki-67 protein expression was significantly higher in Group A as compared with non-TACE group （55.44% ± 13.72% vs 44.43% ± 20.70%, P 〈 0.05）. The PCNA protein expression was significantly higher in Groups A and B as compared with non-TACE group （72.22% ± 8.71% vs 62.92% ± 17.21%, 69.91% ± 13.38% vs 62.92% ± 17.21%, respectively, P 〈0.05）. CONCLUSION： Preoperative multi-material TACE suppresses the proliferation of HCC cells, while a single material embolization and chemotherapy alone enhance the proliferation of HCC cells.

Relationship between apoptosis and invasive and metastatic potential of hepatocellular carcinoma

Objective: To study relationship between apoptosis and invasive and metastatic potential of hepatocellu- lar carcinoma (HCC). Methods: Apoptotic rate (AR), proliferative index (PI) and S-phase fraction (SPF) were measured by flow cytometry, and p170, p21 and nucleoside diphosphate kinase (ndpk) by strept avidin-biotin complex immunohistochemical technique in 57 pa- tients with HCC. Results: In this group, AR was 1.77% ±0.19%, SPF 12.55% ±0.68%, and PI 20.91% ±1.12% (r =-0.173). p170, p21 and ndpk positive rates were 61.36%, 68, 18%, 52.27% respectively in patients with a mean AR of ≤1.77%, and 23.08%, 38.46%, 84.62% respectively in patients with a mean AR of >1.77% (all P<0.05). In patients with positive tumor invasiveness and metastasis, nd- pk (+) was 43.75%, p21 (+) 75.00%, p170 (+) 65.63%, AR 1.12% ±0. 16%, PI 23.78% ±1.48%, and SPF 13.90 % ±0.99 %. In patients with negative invasiveness and metastasis, however, ndpk (+) was 80.00%, p21 (+) 44.00%, p170 (+) 36.00%, AR 2,32%±0.52%, PI 18.53% ±0.82% and SPF 11.43% ±0.70%. Conclusion: Apoptosis of HCC is negatively correla- ted with its invasive and metastatic potential or other factors as proliferative activity, p21, p170 and ndpk.

Comparison of two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma

AIM:To compare two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma.METHODS:Thirty New Zealand rabbits were randomly divided into two groups:A and B.Group A was assigned a traditional laparotomy method(embedding tumor fragments directly into the liver with tweezers).Group B was subjected to an improved laparotomy method(injection of tumor fragments into the liver through a 15 G syringe needle).The operation time, incision length, incision infection rate, and mortality rate were compared between the two groups after laparotomy.Magnetic resonance imaging(MRI) was performed to evaluate tumor formation rates and the characteristics of the tumors 2 wk after laparotomy.RESULTS:The mean operation times for the two groups(Group A vs Group B) were 23.2 ± 3.4 min vs 17.5 ± 2.9 min(P < 0.05); the incision length was 3.3 ± 0.5 cm vs 2.4 ± 0.6 cm(P < 0.05); and the mortality rate after 2 wk was 26.7% vs 0%(P < 0.05); all of these outcomes were significantly different between the two groups.The incision infection rates in the two groups were 6.7% vs 0%(P > 0.05), whichwere not significantly different.MRI performed after 2weeks showed that the tumor formation rates in the two groups were 90.9%vs 93.3%(P>0.05).These rates were not significantly different between the two groups.The celiac implantation rate and abdominal wall metastasis rate in the two groups were 36.4%vs 13.3%(P<0.05)and 27.2%vs 6.7%(P<0.05),respectively,which were significantly different between the two groups.CONCLUSION:The tumor formation rates were not significantly different between the two methods for modeling rabbit VX2 hepatocarcinoma.However,the improved method is recommended because it has certain advantages.

Multiparameter magnetic resonance imaging of liver fibrosis in a bile duct ligation mouse model

BACKGROUND Bile duct ligation(BDL)in animals is a classical method for mimicking cholestatic fibrosis.Although different surgical techniques have been described in rats and rabbits,mouse models can be more cost-effective and reproducible for investigating cholestatic fibrosis.Magnetic resonance imaging(MRI)has made great advances for noninvasive assessment of liver fibrosis.More comprehensive liver fibrotic features of BDL on MRI are important.However,the utility of multiparameter MRI to detect liver fibrosis in a BDL mouse model has not been assessed.AIM To evaluate the correlation between the pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model.METHODS Twenty-eight healthy adult male balb/c mice were randomly divided into four groups:sham,week 2 BDL,week 4 BDL,and week 6 BDL.Multiparameter MRI sequences,included magnetic resonance cholangiopancreatography,T1-weighted,T2-weighted,T2 mapping,and pre-and post-enhanced T1 mapping,were performed after sham and BDL surgery.Peripheral blood and liver tissue were collected after MRI.For statistical analysis,Student’s t-test and Pearson’s correlation coefficient were used.RESULTS Four mice died after BDL surgery;seven,six,five and six mice were included separately from the four groups.Signal intensities of liver parenchyma showed no difference on TI-and T2-weighted images.Bile duct volume,ΔT1 value,T2 value,and the rate of liver fibrosis increased steadily in week 2 BDL,week 4 BDL and week 6 BDL groups compared with those in the sham group(P<0.01).Alanine aminotransferase and aspartate transaminase levels initially surged after surgery,followed by a gradual decline over time.Strong correlations were found between bile duct volume(r=0.84),T2 value(r=0.78),ΔT1 value(r=0.62),and hepatic fibrosis rate(all P<0.01)in the BDL groups.CONCLUSION The BDL mouse model induces changes that can be observed on MRI.The MRI parameters correlate with the hepatic fibrosis rate and allow for detection of cholestatic fibrosis.