Comparing and combining MRE, T1ρ, SWI, IVIM, and DCE-MRI for the staging of liver fibrosis in rabbits: Assessment of a predictive model based on multiparametric MRI.

PURPOSE: To establish and validate an optimal predictive model based on multiparametric MRI for staging liver fibrosis (LF) in rabbits with magnetic resonance elastography (MRE), spin-lattice relaxation time in the rotating frame (T1ρ imaging), SWI, intravoxel incoherent motion (IVIM), and DCE-MRI. METHODS: The LF group included 120 rabbits induced by subcutaneous injections of carbon tetrachloride (CCl4 ); 30 normal rabbits served as the control group. Multiparametric MRI was performed, including MRE, T1ρ, SWI, IVIM, and DCE-MRI. The quantitative parameters were analyzed in two groups, with histopathological results serving as the reference standard. The diagnostic performance of multiparametric MRI and the predictive model established by multivariable logistic regression analysis were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In total, 32, 67, and 51 rabbits were histologically diagnosed as no fibrosis (stage F0), early-stage LF (F1-F2), and advanced-stage LF (F3-F4), respectively. The LF stages presented a strong correlation with liver stiffness (LS) on MRE (r = 0.90), signal-intensity ratio (SIR) on SWI (r = -0.84), and Ktrans on DCE-MRI (r = 0.71; p < 0.05 for all). The LS and SIR parameters had higher AUC values for distinguishing early-stage LF from both no fibrosis (0.94 and 0.93, respectively) and advanced-stage LF (0.95 and 0.87, respectively). The predictive model showed a slightly higher AUC value of 0.97 (0.90-0.99) than LS and SIR in distinguishing early-stage LF from no fibrosis (p > 0.05), a significantly higher AUC value of 0.98 (0.93-0.99) than the SIR in distinguishing early-stage from advanced-stage LF (p < 0.05). CONCLUSION: SWI, DCE-MRI, and MRE in particular showed improved performance for LF diagnosis and stage. The predictive model based on multiparametric MRI was found to further enhance diagnostic accuracy and could serve as an excellent imaging tool for staging LF.

Evaluation of renal ischemia-reperfusion injury by magnetic resonance imaging texture analysis: An experimental study.

PURPOSE: To explore the value of MRI texture analysis in evaluating the presence and severity of early renal ischemia-reperfusion injury (IRI). METHODS: Healthy New Zealand rabbits were used (IRI group, N = 54; control group, N = 8). Rabbits in the IRI group underwent left renal artery clamping for 60 minutes. Magnetic resonance imaging was performed before and at 1, 12, 24, and 48 hours after IRI. The relationship between MRI texture features and histopathology parameters was assessed using Pearson's correlation coefficients. The diagnostic performance of texture features in kidney differentiation at different time points was assessed by receiver operating characteristic curve analysis. RESULTS: T2 WI_S(3,-3)Inverse_Difference_Moment had the strongest correlation with brush border destruction, tubular epithelial edema, necrosis, and cast (r = 0.56, -0.58, 0.62, and 0.69, respectively; all P < .001). BOLD_S(4,-4)Correlation had the strongest correlation with interstitial inflammatory cell infiltration (r = 0.63, P < .001). SWI_S(4,4)Difference_Entropy had the strongest correlation with microvessel density (r = 0.61, P < .001). The areas under the curve for T2 WI_S(3,-3)Inverse_Difference_Moment, SWI_S(4,4)Difference_Entropy, and BOLD_S(4,-4)Correlation in kidney differentiation before IRI and that at 1 and 12 hours after reperfusion were 0.76, 0.72, and 0.70, respectively; the values before IRI and at 24 and 48 hours after reperfusion were 0.84, 0.81, and 0.69, respectively. The area under the curve for T2 WI_S(3,-3)Inverse_Difference_Moment in kidney differentiation at 1 and 12 hours after reperfusion and that at 24 and 48 hours after reperfusion was 0.66. CONCLUSION: Magnetic resonance imaging texture analysis can be used for evaluating the presence and severity of early renal IRI.

Staging liver fibrosis on multiparametric MRI in a rabbit model with elastography, susceptibility-weighted imaging and T1ρ imaging: a preliminary study.

BACKGROUND: Magnetic resonance elastography (MRE), susceptibility-weighted imaging (SWI), and T1ρ are three techniques for staging of liver fibrosis (LF). PURPOSE: To assess the value of MRE, SWI, and T1ρ imaging in staging LF. MATERIAL AND METHODS: Sixty rabbits were injected with 50% CCl4oil solution, whereas 20 rabbits were given normal saline. All rabbits underwent pathological examination to determine LF stages. The liver stiffness (LS), liver-to-muscle signal intensity ratio (SIR), and T1ρ values were measured from MRE, SWI, and T1ρ imaging, respectively. RESULTS: The number of rabbits was 14, 11, 10, 9, and 11 for F0, F1, F2, F3, and F4, respectively. LS (r = 0.91) and T1ρ (r = 0.51) positively correlated with LF stages, while negative correlation was present for SIR (r = -0.81). Among the three parameters, the LS values revealed the best diagnostic efficacy in staging LF, with an AUC value of 0.95 for ≥F1, 0.95 for ≥F2, 0.99 for ≥F3, and 0.98 for ≥F4. The combination of LS and SIR could best predict LF stages ≥F1, ≥F2, ≥F3 and ≥F4, with AUC values of 0.97, 0.98, 0.99, and 0.99, respectively, which were greater than those of the other two-paired parameters. A multiparametric analysis showed that the combination of all three parameters had AUC values of 0.97, 0.98, 1.00, and 1.00 for staging ≥F1, ≥F2, ≥F3, and ≥F4, respectively. CONCLUSION: Multiparametric MR imaging was superior to individual imaging for LF staging.

Diagnostic Efficacy of Contrast-Enhanced MRI in Detecting Residual or Recurrent Hepatocellular Carcinoma After Transarterial Chemoembolization: A Systematic Review and Meta-analysis.

BACKGROUND: The diagnostic efficacy of contrast-enhanced magnetic resonance imaging (CEMRI) in diagnosing residual or recurrent hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) is currently not completely clear. PURPOSE: To investigate the diagnostic efficacy of CEMRI in detecting residual or recurrent HCCs after TACE by meta-analysis. STUDY TYPE: Systematic review and meta-analysis. POPULATION: A systematic literature search was performed in PubMed, Embase, Web of Science, Ovid, and the Cochrane Library database up to June 2019 to find original studies on diagnosing patients suspected of residual or recurrent HCCs after TACE with CEMRI. Thirteen studies comprising 721 nodules were finally included. FIELD STRENGTH/SEQUENCE: 1.5T or 3.0T, CEMRI. ASSESSMENT: Quality assessment of the included studies was performed by applying the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. STATISTICAL TESTS: Sensitivity and specificity were pooled with a bivariate random-effects model. Heterogeneity was assessed by the chi-square test. The potential sources of heterogeneity were explored by subgroup and publication bias analyses. RESULTS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic (ROC) curve (AUC) of CEMRI in diagnosing residual or recurrent HCCs after TACE were 91% (95% confidence interval [CI]: 87%-96%), 93% (95% CI: 85%-97%), 12.22 (95% CI: 5.62-26.57), 0.09 (95% CI: 0.05-0.18), 126.99 (95% CI: 34.76-436.99) and 0.97 (95% CI: 0.95-0.98), respectively. Subgroup analysis revealed that CEMRI performed significantly better in prospective studies than in retrospective studies: 0.99 (95% CI: 0.96-1.00) vs. 0.95 (95% CI: 0.92-0.96) with P < 0.05. DATA CONCLUSION: Our meta-analysis suggested that CEMRI had high diagnostic efficacy in detecting residual or recurrent HCCs after TACE and may serve as an alternative method for further evaluation after TACE. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;52:1019-1028.

Long non-coding RNA LINC-PINT attenuates paclitaxel resistance in triple-negative breast cancer cells via targeting the RNA-binding protein NONO.

The treatment of triple-negative breast cancer (TNBC) relies largely on chemotherapies. However, it is frequent that TNBC patients develop resistance to the chemotherapy drugs. Generation of drug-resistant cell lines facilitates the identification of drug resistance. Here, we established two paclitaxel (PTX)-resistant TNBC cancer cell lines using an intermittent and stepwise method and found that long non-coding RNA long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) was significantly decreased in PTX-resistant cancer cells. Ectopic expression of LINC-PINT sensitized both PTX-resistant TNBC and wild-type TNBC to PTX. Moreover, RNA immunoprecipitation showed that LINC-PINT bound to RNA-binding protein NONO. Overexpression of LINC-PINT resulted in the degradation of NONO in a proteasome-dependent manner and vice versa. Knockdown of NONO with siRNA sensitized TNBC to PTX. We further analyzed the expression level of LINC-PINT and NONO in patient samples via online database and found that LINC-PINT and NONO may function antagonistically in all types of breast cancers. Taken together, our data illustrated a tumor suppressor role of LINC-PINT in sensitizing TNBC to chemotherapies via destabilizing NONO.

Hybrid sequencing of the Gynostemma pentaphyllum transcriptome provides new insights into gypenoside biosynthesis.

BACKGROUND: Gypenosides are a group of triterpene saponins from Gynostemma pentaphyllum that are the same as or very similar to ginsenosides from the Panax species. Several enzymes involved in ginsenoside biosynthesis have been characterized, which provide important clues for elucidating the gypenoside biosynthetic pathway. We suppose that gypenosides and ginsenosides may have a similar biosynthetic mechanism and that the corresponding enzymes in the two pathways may have considerable similarity in their sequences. To further understand gypenoside biosynthesis, we sequenced the G. pentaphyllum transcriptome with a hybrid sequencing-based strategy and then determined the candidate genes involved in this pathway using phylogenetic tree construction and gene expression analysis. RESULTS: Following the PacBio standard analysis pipeline, 66,046 polished consensus sequences were obtained, while Illumina data were assembled into 140,601 unigenes with Trinity software. Then, these output sequences from the two analytical routes were merged. After removing redundant data with CD-HIT software, a total of 140,157 final unigenes were obtained. After functional annotation, five 2,3-oxidosqualene cyclase genes, 145 cytochrome P450 genes and 254 UDP-glycosyltransferase genes were selected for the screening of genes involved in gypenoside biosynthesis. Using phylogenetic analysis, several genes were divided into the same subfamilies or closely related evolutionary branches with characterized enzymes involved in ginsenoside biosynthesis. Using real-time PCR technology, their expression patterns were investigated in different tissues and at different times after methyl jasmonate induction. Since the genes in the same biosynthetic pathway are generally coexpressed, we speculated that GpOSC1, GpCYP89, and GpUGT35 were the leading candidates for gypenoside biosynthesis. In addition, six GpWRKYs and one GpbHLH might play a possible role in regulating gypenoside biosynthesis. CONCLUSIONS: We developed a hybrid sequencing strategy to obtain longer length transcriptomes with increased accuracy, which will greatly contribute to downstream gene screening and characterization, thus improving our ability to elucidate secondary metabolite biosynthetic pathways. With this strategy, we found several candidate genes that may be involved in gypenoside biosynthesis, which laid an important foundation for the elucidation of this biosynthetic pathway, thus greatly contributing to further research in metabolic regulation, synthetic biology and molecular breeding in this species.

Evaluation of renal dysfunction using texture analysis based on DWI, BOLD, and susceptibility-weighted imaging.

OBJECTIVE: To explore the value of texture analysis based on diffusion-weighted imaging (DWI), blood oxygen level-dependent MRI (BOLD), and susceptibility-weighted imaging (SWI) in evaluating renal dysfunction. METHODS: Seventy-two patients (mean age 53.72 ± 13.46 years) underwent MRI consisting of DWI, BOLD, and SWI. According to their estimated glomerular filtration rate (eGFR), the patients were classified into either severe renal function impairment (sRI, eGFR < 30 mL/min/1.73 m2), non-severe renal function impairment (non-sRI, eGFR ≥ 30 mL/min/1.73 m2, and < 80 mL/min/1.73 m2), or control (CG, eGFR ≥ 80 mL/min/1.73 m2) groups. Thirteen texture features were extracted and then were analyzed to select the most valuable for discerning the three groups with each imaging method. A ROC curve was performed to compare the capacities of the features to differentiate non-sRI from sRI or CG. RESULTS: Six features proved to be the most valuable for assessing renal dysfunction: 0.25QuantileDWI, 0.5QuantileDWI, HomogeneityDWI, EntropyBOLD, SkewnessSWI, and CorrelationSWI. Three features derived from DWI (0.25QuantileDWI, 0.5QuantileDWI, and HomogeneityDWI) were smaller in sRI than in non-sRI; EntropyBOLD and CorrelationSWI were smaller in non-sRI than in CG (p < 0.05). 0.25QuantileDWI, 0.5QuantileDWI, and HomogeneityDWI showed similar capacities for differentiating sRI from non-sRI. Similarly, EntropyBOLD and CorrelationSWI showed equal capacities for differentiating non-sRI from CG. CONCLUSION: Texture analysis based on DWI, BOLD, and SWI can assist in assessing renal dysfunction, and texture features based on BOLD and SWI may be suitable for assessing renal dysfunction during early stages. KEY POINTS: • Texture analysis based on MRI techniques allowed for assessing renal dysfunction. • Texture features based on BOLD and SWI, but not DWI, may be suitable for assessing renal function impairment during early stages. • SWI exhibited a similar capacity to BOLD for assessing renal dysfunction.

[Value of susceptibility weighted imaging in hepatic fibrosis staging by using MR in a rabbit model].

OBJECTIVE: To assess the feasibility of susceptibility weighted imaging (SWI) in staging hepatic fibrosis(HF). METHODS: Sixty healthy rabbits were divided into three groups: HF group(n=32), control group(n=16), supplementary group(n=12). Rabbits in HF group and supplementary group were injected subcutaneously with 50% CCl4 oil solution to establish hepatic fibrosis model. On the basis of preliminary test, eight rabbits from HF group and four rabbits from control group underwent liver conventional MR scans and SWI once a time at 4, 5, 6, 10 weeks after CCl4 administration.After MR scans at each time point, rabbits were killed to detect pathological staging with Scheuer staging.The liver signal intensity (SI) and liver-to-muscle SI ratios (SIR) were measured. According to the Scheuer classification of histological fibrosis stages, the correlation about the SI value, SIR value and the histological fibrosis stages was investigated by using the Spearman correlation test. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of SWI for staging HF on the basis of the histopathologic analysis of HF. RESULTS: There were fifteen rabbits in pathological staging F0, the value of SIR and SI was 0.974 ± 0.018, 374±44, SIR values of pathological staging from F1 to F4 were 0.963 ± 0.018, 0.796 ± 0.023, 0.786 ± 0.025, 0.512±0.024 respectively. SI values of pathological staging from F1 to F4 were 372±18, 376±22, 346±15, 288±19 respectively. In the early period of liver fibrosis, there were no statistical differences in the SI value between F0 and F1, F1 and F2 stage.With progression of hepatic fibrosis, from F2 to F4, SI value decreased, the difference was statistically significant (P<0.05). With the progress of liver fibrosis, SIR value was reduced. It was negatively correlated with the HF stages and SIR value(r=-0.896, P<0.05). ROC curve analysis showed that the efficiency of SI value diagnosis in liver fibrosis was high in the late stage of liver fibrosis, but it was low in the early stage.The performance of liver-to-muscle SI ratio on SWI was high in the early stage. Liver-to-muscle SI ratio had a higher diagnostic performance than SI in the diagnosis of liver fibrosis stages. CONCLUSION: SWI can be a safe, reliable method for staging hepatic fibrosis and provide quantitative imaging basis for clinical treatment.

[Advance in transcriptomic studies of ginseng species].

There are many valuable medicinal plants in Ginseng genus belonging to Araliaceae. Among them, Panax ginseng, P. quinquefolium and P. notoginseng are the most famous species. With the development of next-generation sequencing (NGS) technologies, sequencing and analysis of transcriptomes have become powerful tools for discovery of novel genes, screening molecular markers and elucidation of specific biosynthetic pathway of secondary metabolites. Their transcriptomes provided abundant genes for further study on functional genomics. Here this paper summarized the recent advances in the transcriptomic studies of these three medicinal plants, including discovery of novel genes and elucidation of metabolic regulation, which will contribute to functional genomics in ginseng species.

[Key technologies in synthetic biology of natural products].

Natural products with complex and diverse structures are the major sources of new drugs. The biosynthesis of natural products is considered to be one of the best ways to solve the problems of complex and scarce natural products. DNA assembly technology and genome editing technology are two key technologies in the emerging interdisciplinary field of synthetic biology. A number of novel DNA assembly methods developed in the last few years have paved the way for the engineering of high molecular weight DNA molecules, including whole genomes, hence, it can realize the reconstruction of the metabolic pathways and speed up optimization process. A wide variety of new tools for microbial genome editing will be applied widely to modify the chassis genome to increase its adaptation with the exogenetic pathways. This article summarized the latest advance with respect to DNA assembly and genome editing, which aims to provide help for reconstruction and optimization of the synthetic biological systems of natural products.

[Strategies of elucidation of biosynthetic pathways of natural products].

Elucidation of the biosynthetic pathways of natural products is not only the major goal of herb genomics, but also the solid foundation of synthetic biology of natural products. Here, this paper reviewed recent advance in this field and put forward strategies to elucidate the biosynthetic pathway of natural products. Firstly, a proposed biosynthetic pathway should be set up based on well-known knowledge about chemical reactions and information on the identified compounds, as well as studies with isotope tracer. Secondly, candidate genes possibly involved in the biosynthetic pathway were screened out by co-expression analysis and/or gene cluster mining. Lastly, all the candidate genes were heterologously expressed in the host and then the enzyme involved in the biosynthetic pathway was characterized by activity assay. Sometimes, the function of the enzyme in the original plant could be further studied by RNAi or VIGS technology. Understanding the biosynthetic pathways of natural products will contribute to supply of new leading compounds by synthetic biology and provide "functional marker" for herbal molecular breeding, thus but boosting the development of traditional Chinese medicine agriculture.

[Advance in flavonoids biosynthetic pathway and synthetic biology].

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health.

[Recent advances in biosynthetic pathway and synthetic biology of taxol].

Taxol, a kind of terpenoid secondary metabolite produced by Taxus brevifolia, is an effective anticancer drug that manufacture relies mainly on the extraction form plants. In order to solve the resource shortage, a lot of work has been done to develop the alternative method. Recently, using synthetic biology to realize heterologous biosynthesis of the precursors of taxol has become a hotspot. Now, the basic framework of taxol biosynthetic pathways has been confirmed, and most enzyme genes involved in taxol biosynthesis have been cloned and identified. The two taxol precursors, taxa-4(5),11(12)-diene and taxa-4(20),11(12)-dien-5α-ol, have been synthesized in Escherichia coli and Saccharomyces cerevisiae. Here this paper reviewed the recent advances in the biosynthetic pathway of taxol and the latest developments of synthetic biology, which aims to provide a guidance for the heterologous biosynthesis of taxol.

[Advance in biosynthesis of terpenoid indole alkaloids and its regulation in Catharanthus roseus].

Catharanthus roseus can produce a variety of terpenoid indole alkaloids (TIA), most of which exhibit strong pharmacological activities. Hence, biosynthesis and regulation of TIA have received recent attention. 3α (S)-strictosidine is an important node in TIA biosynthesis, which is a condensation product of secologanin and tryptamine. The former is produced in iridoid pathway, and the latter is produced in indole pathway. Vindoline and catharanthine, which are produced respectively by 3α (S)-strictosidine via multi-step enzymatic reaction, can form α-3, 4-anhydrovinblastine by the condensation reaction. Then, vinblastine and vincristine are generated from α-3, 4-anhydrovinblastine. Many transcription factors are involved in the regulation of TIA synthesis, such as AP2/ERF and WRKY. Illumination of biosynthetic pathway has laid a foundation for the study of synthetic biology. Today, 3α (S)-strictosidine and vindoline have been synthesized in heterologous hosts Saccharomyces cerevisiae.Research about synthetic biology and the regulation mechanisms will provide a guidance for the production and development of TIA drugs in C. roseus.

Multiparametric MRI-based whole-liver radiomics for predicting early-stage liver fibrosis in rabbits.

OBJECTIVES: To develop and validate a whole-liver radiomic model using multiparametric MRI for predicting early-stage liver fibrosis (LF) in rabbits. METHODS: A total of 134 rabbits (early-stage LF, n = 91; advanced-stage LF, n = 43) who underwent liver magnetic resonance elastography (MRE), hepatobiliary phase, dynamic contrast enhanced (DCE), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging, and T2* scanning were enrolled and randomly allocated to either the training or validation cohort. Whole-liver radiomic features were extracted and selected to develop a radiomic model and generate quantitative Rad-scores. Then, multivariable logistic regression was utilized to determine the Rad-scores associated with early-stage LF, and effective features were integrated to establish a combined model. The predictive performance was assessed by the area under the curve (AUC). RESULTS: The MRE model achieved superior AUCs of 0.95 in the training cohort and 0.86 in the validation cohort, followed by the DCE-MRI model (0.93 and 0.82), while the IVIM model had lower AUC values of 0.91 and 0.82, respectively. The Rad-scores of MRE, DCE-MRI and IVIM were identified as independent predictors associated with early-stage LF. The combined model demonstrated AUC values of 0.96 and 0.88 for predicting early-stage LF in the training and validation cohorts, respectively. CONCLUSIONS: Our study highlights the remarkable performance of a multiparametric MRI-based radiomic model for the individualized diagnosis of early-stage LF. ADVANCES IN KNOWLEDGE: This is the first study to develop a combined model by integrating multiparametric radiomic features to improve the accuracy of LF staging.

Effect of Iron Deposition on Native T1 Mapping and Blood Oxygen Level Dependent for the Assessment of Liver Fibrosis in Rabbits With Carbon Tetrachloride Intoxication.

RATIONALE AND OBJECTIVES: This study aimed to explore the effect of iron deposition on native T1 mapping and blood oxygen level-dependent (BOLD) imaging in detecting liver fibrosis (LF) in a rabbit model. MATERIALS AND METHODS: An LF group (n = 100) was established by subcutaneously injecting 50% carbon tetrachloride (CCl4) oil solution, and 20 normal rabbits composed a control group. Native T1 mapping and BOLD were performed, and the T1native and R2* quantitative parameters were analyzed by receiver operating characteristic (ROC) and multiple logistic regression analyses, with histopathological results and liver iron content (LIC) serving as reference standards. RESULTS: In total, 18, 17, 16, 18, and 15 rabbits were histopathologically diagnosed with LF stages F0, F1, F2, F3, and F4, respectively. T1native (r = 0.47), R2* (r = 0.75) and LIC (r = 0.61) increased with LF stage progression (p < 0.001). Compared to T1native values, R2* performed better in diagnosing the LF stage, especially for distinguishing F1-F2 from F3-F4 (AUC = 0.66 vs. 0.91, p = 0.01). Combined with the LIC, both T1native and R2* showed improved diagnostic value in comparison to the individual imaging techniques, particularly for diagnosing F0 vs. F1-F2 and F0 vs. F1-F4, with AUC values of 0.90 vs. 0.70 (p = 0.01) and 0.93 vs. 0.77 (p = 0.01) for T1native + LIC vs. LIC, respectively. CONCLUSION: BOLD imaging performed better than native T1 mapping in predicting and diagnosing LF stage progression. The decrease in diagnostic accuracy caused by the deposition of liver iron is a potential pitfall in the assessment of LF with BOLD imaging and native T1 mapping.

Simultaneous liver steatosis, fibrosis and iron deposition quantification with mDixon quant based on radiomics analysis in a rabbit model.

PURPOSE: To evaluate the feasibility of simultaneous quantification of liver fibrosis, liver steatosis and abnormal iron deposition using mDixon Quant based on radiomics analysis, and to eliminate the interference among different histopathologic features. METHODS: One hundred and twenty rabbits that were administered CCl4 for 4-16 weeks and a cholesterol rich diet for the initial 4 weeks in the experimental group and 20 rabbits in the control group were examined using mDixon. Radiomics features of the whole liver were extracted from PDFF and R2* and radiomics models for discriminating steatosis: S0-S1 vs. S2-S4, fibrosis: F0-F2 vs. F3-F4 and iron deposition: normal vs. abnormal were constructed respectively and evaluated using receiver operating characteristic (ROC) curves with the histopathological results as reference standard. Combined corrected models merging the radscore and the other two histopathologic features were evaluated using multiple logistic regression analyses and compared with radiomics models. RESULTS: The area under the ROC curve (AUC) of the radiomics model with PDFF features was 0.886 and 0.843 in the training and the test set, respectively, for the diagnosis of liver steatosis grade S0-1 and S2-S4. The radiomics model based on R2* features were 0.815 and 0.801 for distinguishing F0-F2 and F3-F4 and 0.831 and 0.738 for discriminating abnormal iron deposition in the training and test set, respectively. The corrected model for liver steatosis and fibrosis (0.944 and 0.912 in the test set) outperformed the radiomics models by eliminating the interference of histopathologic features(P < 0.05), but had comparable diagnostic performance for abnormal iron deposition(P > 0.05). CONCLUSIONS: It is feasible for mDixon to simultaneously quantify whole liver steatosis, fibrosis and iron deposition based on radiomics analysis. It is valuable to minimize the interference of different pathological features for the assessment of liver steatosis and fibrosis.

Dynamic contrast-enhanced MRI with Gd-EOB-DTPA for the quantitative assessment of early-stage liver fibrosis induced by carbon tetrachloride in rabbits.

PURPOSE: To explore quantitative parameters obtained by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with Gd-EOB-DTPA in discriminating early-stage liver fibrosis (LF) in a rabbit model. MATERIALS AND METHODS: LF was established in 60 rabbits by the injection of 50% CCl4 oil solution, whereas 30 rabbits served as the control group. All rabbits underwent pathological examination to determine the LF stage using the METAVIR classification system. DCE MRI was performed, and quantitative parameters, including Ktrans, Kep, Ve, Vp and Re were measured and evaluated among the different LF stages using spearman correlation coefficients and receiver operating characteristic curve. RESULTS: In all, 24, 25, and 22 rabbits had stage F0, stage F1, and stage F2 LF, respectively. Ktrans (r = 0.803) increased, and Kep (r = -0.495) and Re (r = -0.701) decreased with LF stage progression (P < 0.001), while no significant correlation was found for Ve or Vp. Ktrans and Re were significantly different between all LF stage pairs compared (F0 vs. F1, F0 vs. F2, F1 vs. F2, F0 vs. F1-F2, P < 0.05). With the exception of F0 vs. F1, Kep differed significantly between stages (P < 0.05). The AUC of Ktrans was higher than that of other quantitative parameters, with an AUC of 0.92, 0.99, 0.94 and 0.92 for staging F0 vs. F1, F0 vs. F2, F1 vs. F2, and F0 vs. F1-F2, respectively. CONCLUSION: Among quantitative parameters of Gd-EOB-DTPA DCE MRI, Ktrans was the best predictor for quantitatively differentiating early-stage LF.

Collagen deposition in the liver is strongly and positively associated with T1rho elongation while fat deposition is associated with T1rho shortening: an experimental study of methionine and choline-deficient (MCD) diet rat model.

BACKGROUND: A number of questions concerning the histological mechanism of elongated T1rho in liver fibrosis remain unanswered. Using a rat model of non-alcoholic fatty liver disease (NAFLD) induced with methionine and choline-deficient (MCD) diet, the primary aim of this study is to clarify whether collagen deposition per se causes liver T1rho elongation. METHODS: There were 45 rats in the NAFLD model group and 8 rats in the control group. NAFLD model rats were fed MCD diet for 1, 2, 4, 6, 8, or 10 weeks, respectively. At the endpoint, the rats had in vivo MRI at 3.0 T and followed by histology. For T1rho data acquisition, a rotary echo spin-lock pulse was implemented in a three-dimensional fast field echo sequence with frequency selective fat suppression. The spin-lock frequency was set to 500 Hz, and the spin-lock times of 5, 10, 40, and 50 ms were used. Liver specimens were processed with hematoxylin-eosin staining for steatosis and inflammation evaluation, and Masson's trichrome staining for collagen visualization. The semiquantitative histopathological evaluation was based on NASH Clinical Research Network criteria. Histomorphometric analysis calculated percentages of fat and collagen accumulations in the livers. RESULTS: A strong (r=0.82) and significant (P<0.0001) positive correlation between liver collagen content and liver T1rho was observed. Rats with no or minimal inflammation could have very long T1rho value. Among experimental rats without a positive fibrosis grading, five rats did not have an inflammation score (i.e., had minimal inflammation or no inflammation) while four had a positive inflammation score; the difference in liver T1rho between these two types of rats was minimal. Eight control rat livers and 15 stage-1 fibrosis rat livers were separated by liver T1rho completely. When four subgroups of experiment rats were selected where the liver collagen had a very narrow range within these subgroups, all these four subgroups showed a trend of negative correlation between liver fat and liver T1rho. CONCLUSIONS: Collagen deposition in the live strongly contributes to liver T1rho elongation, while fat deposition contributes to T1rho shortening. In a well-controlled experimental setting, T1rho measure alone allows separation of healthy livers and stage-1 liver fibrosis in the MCD rat liver model.

Diffusion tensor imaging study of the anterior limb of internal capsules in neuroleptic-naive schizophrenia.

RATIONALE AND OBJECTIVES: Abnormalities in brain structure have been implicated in psychosis. Herein, we investigated the differences in fractional anisotropy (FA) and average diffusion coefficient (ADC) in the bilateral anterior limb of internal capsules between neuroleptic-naive schizophrenic patients and appropriately matched healthy controls. MATERIALS AND METHODS: Magnetic resonance imaging was performed with a 1.5 T superconductive MR scanner, and diffusion tensor imaging was carried out in 21 neuroleptic-naive schizophrenic patients and 18 matched healthy controls. FA and ADC were measured by region of interest analysis. RESULTS: Compared with healthy controls, the neuroleptic-naive schizophrenic patients showed significantly reduced FA in the bilateral anterior limb of the internal capsule. However, the difference in the ADC values between the patients and the controls was not significant. CONCLUSIONS: FA of the bilateral anterior limb of the internal capsule was reduced in neuroleptic-naive schizophrenic patients, indicating that the integrity of the white matter of the bilateral thalamus-frontal connection or the bilateral thalamus-anterior cingulate gyrus connection was destroyed.