Protective effect of Achyranthes aspera against compound 48/80, histamine and ovalbumin-induced allergic disorders in murine model.

BACKGROUND: Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed. METHODS AND RESULTS: Three extracts of A. aspera [aqueous (AaAq), hydroalcoholic (AaHA), ethanolic (AaEt)] were evaluated for their potency against C48/80-induced anaphylaxis in mice at 200 mg/kg BW oral dose. The effective dose of the most potent extract was determined through its effect on C48/80-induced anaphylaxis, and was further analyzed through its effect on mast cell degranulation, histamine-induced bronchospasm and ovalbumin (OVA)-induced asthma in a murine model. Among the three extracts, AaAq was found to be most potent at 200 mg/kg BW. AaAq 400 (400 mg/kg BW) was found to be the most effective dose in terms of inhibition of mortality and histamine level. AaAq 400 prevented the peritoneal and mesenteric mast cells from undergoing morphological changes due to degranulation induced by C48/80. Further, AaAq 400 delayed pre-convulsive time in histamine-induced bronchospasm. In the OVA-induced asthma model, AaAq 400 inhibited the level of inflammatory cell count in blood, bronchoalveolar lavage fluid and peritoneal fluid of mice. The Th2 cytokines (IL-4, IL-5, IL-13), TGF-ß and OVA-specific IgE were also reduced as evaluated by ELISA. Also, significant reduction in IL-5 (an eosinophilia indicator) transcript abundance and lung inflammatory score was observed. AaAq was safe up to 4000 mg/kg BW. CONCLUSIONS: Thus AaAq 400 possesses significant antiallergic potential and acts via attenuation of C48/80-induced anaphylaxis and inhibition of mast cell degranulation. It reduces pre-convulsive dyspnea in histamine-induced bronchospasm and Th2 cytokines in asthmatic mice.

Integrating baseline MR imaging biomarkers into BCLC and CLIP improves overall survival prediction of patients with hepatocellular carcinoma (HCC).

OBJECTIVES: We aimed to evaluate the independent predictive role of baseline imaging biomarkers for overall survival (OS) and transplant-free survival (TFS) in patients with HCC and assess the incremental value of these biomarkers to current staging systems. METHODS: In this retrospective IRB approved study, the clinical, laboratory, and imaging parameters of 304 HCC patients were collected. Cox regression model was utilized to identify the potential predictors of survival. Recursive partitioning test was utilized to identify the optimal ADC cutoff for stratifying patients' OS. Patients were stratified based on Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Binary ADC value (above vs. below the cutoff) and tumor margin (well- vs. ill-defined) were integrated into BCLC and CLIP. OS and TFS was compared for patients based on standard criteria with and without imaging biomarkers. RESULTS: At baseline, patients with low tumor ADC and well-defined tumor margin (favorable imaging biomarkers) had longer survival, as compared to those with high ADC and ill-defined tumor margin (unfavorable imaging biomarkers) (median OS of 43 months vs. 7 months, respectively) (p < 0.001). Tumor ADC and tumor margin remained strong independent predictors of survival after adjustment for demographics, BCLC and CLIP staging, and tumor burden. Incorporating ADC and tumor margin improved performance of OS prediction by 9% in BCLC group and 6% in CLIP group. CONCLUSION: Incorporating ADC and tumor margin to current staging systems for HCC significantly improve prediction of OS and TFS of these criteria. KEY POINTS: • ADC and tumor margin are predictors of overall survival in HCC patients, independent of clinical, laboratory, and other imaging variables. • Adding ADC and tumor margin improved the prognostic value of BCLC and CLIP criteria by 9% and 6%, respectively. • High ADC and ill-defined tumor margin at baseline predicted poor survival, regardless of patient's liver function and general health status.

Post-TACE changes in ADC histogram predict overall and transplant-free survival in patients with well-defined HCC: a retrospective cohort with up to 10 years follow-up.

OBJECTIVES: To evaluate the role of change in apparent diffusion coefficient (ADC) histogram after the first transarterial chemoembolization (TACE) in predicting overall and transplant-free survival in well-circumscribed hepatocellular carcinoma (HCC). METHODS: Institution database was searched for HCC patients who got conventional TACE during 2005-2016. One hundred four patients with well-circumscribed HCC and complete pre- and post-TACE liver MRI were included. Volumetric MRI metrics including tumor volume, mean ADC, skewness, and kurtosis of ADC histograms were measured. Univariate and multivariable Cox models were used to test the independent role of change in imaging parameters to predict survival. P values < 0.05 were considered significant. RESULTS: In total, 367 person-years follow-up data were analyzed. After adjusting for baseline liver function, tumor volume, and treatment modality, incremental percent change in ADC (ΔADC) was an independent predictor of longer overall and transplant-free survival (p = 0.009). Overall, a decrease in ADC-kurtosis (ΔkADC) showed a strong role in predicting longer survival (p = 0.021). Patients in the responder group (ΔADC ≥ 35%) had the best survival profile, compared with non-responders (ΔADC < 35%) (p < 0.001). ΔkADC, as an indicator of change in tissue homogeneity, could distinguish between poor and fair survival in non-responders (p < 0.001). It was not a measure of difference among responders (p = 0.244). Non-responders with ΔkADC ≥ 1 (homogeneous post-TACE tumor) had the worst survival outcome (HR = 5.70, p < 0.001), and non-responders with ΔkADC < 1 had a fair survival outcome (HR = 2.51, p = 0.029), compared with responders. CONCLUSIONS: Changes in mean ADC and ADC kurtosis, as a measure of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in well-circumscribed HCC, in order to monitor early response to TACE and identify patients with treatment failure and poor survival outcome. KEY POINTS: • Changes in the mean and kurtosis of ADC histograms, as the measures of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in patients with well-defined HCC. • A ≥ 35% increase in volumetric ADC after TACE is an independent predictor of good survival, regardless of the change in ADC histogram kurtosis. • In patients with < 35% ADC change, a decrease in ADC histogram kurtosis indicates partial response and fair survival, while ∆kurtosis ≥ 1 correlates with the worst survival outcome.

Baseline 3D-ADC outperforms 2D-ADC in predicting response to treatment in patients with colorectal liver metastases.

OBJECTIVES: To examine the value of baseline 3D-ADC and to predict short-term response to treatment in patients with hepatic colorectal metastases (CLMs). METHODS: Liver MR images of 546 patients with CLMs (2008-2015) were reviewed retrospectively and 68 patients fulfilled inclusion criteria. Patients had received systemic chemotherapy (n = 17), hepatic trans-arterial chemoembolization or TACE (n = 34), and 90Y radioembolization (n = 17). Baseline (pre-treatment) 3D-ADC (volumetric) of metastatic lesions was calculated employing prototype software. RECIST 1.1 was used to assess short-term response to treatment. Prediction of response to treatment by baseline 3D-ADC and 2D-ADC (ROI-based) was also compared in all patients. RESULTS: Partial response to treatment (minimum 30% decrease in tumor largest transverse diameter) was seen in 35.3% of patients; 41.2% with systemic chemotherapy, 32.4% with TACE, and 35.3% with 90Y radioembolization (p = 0.82). Median baseline 3D-ADC was significantly lower in responding than in nonresponding lesions. Area under the curve (AUC) of 3D-ADC was 0.90 in 90Y radioembolization patients, 0.88 in TACE patients, and 0.77 in systemic chemotherapy patients (p < 0.01). Optimal prediction was observed with the 10th percentile of ADC (1006 × 10-6 mm2/s), yielding sensitivity and specificity of 77.4% and 91.3%, respectively. 3D-ADC outperformed 2D-ADC in predicting response to treatment (AUC; 0.86 vs. 0.71; p < 0.001). CONCLUSION: Baseline 3D-ADC is a highly specific biomarker in predicting partial short-term response to treatment in hepatic CLMs. KEY POINTS: • Baseline 3D-ADC is a highly specific biomarker in predicting response to different treatments in hepatic CLMs. • The prediction level of baseline ADC is better for90Y radioembolization than for systemic chemotherapy/TACE in hepatic CLMs. • 3D-ADC outperforms 2D-ADC in predicting short-term response to treatment in hepatic CLMs.

Does the change in volumetric functional MR metrics post-TACE predict histopathologic grading of hepatocellular carcinoma?

OBJECTIVES: To evaluate whether the change in volumetric ADC (vADC) and volumetric venous enhancement (vVE) after transarterial chemoembolization (TACE) can predict the histologic grading of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This HIPPA-compliant retrospective study was approved by our institutional review board. The study population included 106 HCC patients (147 index lesions) who had MR imaging within 3 months before and after TACE and pathologic report of the HCC either by biopsy or liver transplantation/resection between 2001 and 2017. Volumetric measurements of venous enhancement (VE) and apparent diffusion coefficient (ADC) were performed on baseline and post-TACE MRI. The tumors were histologically classified into two low-grade and high-grade groups. The parameters between two groups were compared using bivariate and multivariate analyses. RESULTS: Median change in vADC, vVE, and absolute vADC skewness after TACE was higher in low-grade HCCs as compared with high-grade HCCs (p < 0.001, p = 0.005, p = 0.04, respectively). Combining ΔvADC, ΔvVE, and the etiology for background liver disease in multivariate analysis had the highest accuracy in distinguishing high-grade tumors (AUC = 91%). CONCLUSION: ΔvADC and ΔvVE after TACE are potential predictors of HCC histopathological grading. Combining functional MRI biomarkers with the etiology of liver disease can enhance the accuracy in assessing degree of differentiation. KEY POINTS: • Change in volumetric functional MRI biomarkers after TACE can be a non-invasive method to evaluate tumor histopathology in HCC. • The etiology of background liver disease might be a predictor of tumor degree of differentiation.

Role of baseline volumetric functional MRI in predicting histopathologic grade and patients' survival in hepatocellular carcinoma.

OBJECTIVES: We aimed to evaluate the role of volumetric ADC (vADC) and volumetric venous enhancement (vVE) in predicting the grade of tumor differentiation in hepatocellular carcinoma (HCC). METHODS: The study population included 136 HCC patients (188 lesions) who had baseline MR imaging and histopathological report. Measurements of vVE and vADC were performed on baseline MRI. Tumors were histologically classified into low-grade and high-grade groups. The parameters between the two groups were compared using Mann-Whitney U and chi-square tests for continuous and categorical parameters, respectively. Area under receiver operating characteristic (AUROC) was calculated to investigate the accuracy of vADC and vVE. Logistic regression and multivariable Cox regression were used to unveil the potential parameters associated with high-grade HCC and patient's survival, respectively. RESULTS: Lesions with higher vADC values and a higher absolute vADC skewness were more likely to be high grade on histopathology assessment (p = 0.001 and p = 0.0291, respectively). Also, vVE showed a trend to be higher in low-grade lesions (p = 0.079). Adjusted multivariable model including vADC, vVE, and vADC skewness could strongly predict HCC degree of differentiation (AUROC = 83%). Additionally, a higher Child-Pugh score (HR = 2.39 [p = 0.02] for score 2 and HR = 3.47 [p = 0.001] for score 3), vADC skewness (HR = 1.52, p = 0.02; per increments in skewness), and tumor volume (HR = 1.1, p = 0.001; per 100 cm3 increments) showed the highest association with patients' survival. CONCLUSIONS: vADC and vVE have the potential to accurately predict HCC differentiation. Additionally, some imaging features in combination with patients' clinical characteristics can predict patient survival. KEY POINTS: • Volumetric functional MRI metrics can be considered as non-invasive measures for determining tumor histopathology in HCC. • Estimating patient survival based on clinical and imaging parameters can be used for modifying management approach and preventing unnecessary adverse events.

Comparison between ROI-based and volumetric measurements in quantifying heterogeneity of liver stiffness using MR elastography.

OBJECTIVES: This study was conducted to quantify the heterogeneity of liver stiffness (LS) on MR elastography (MRE) by comparing ROI-based and volumetric measurements. METHODS: LS was measured by ROI-based and volumetric segmentation of the liver parenchyma. Mean LS (MLS) was calculated and used to assign stages of fibrosis. Volumetric measurements of stiffness maps were used to determine the percentage of liver volume above/below MLS and presence of LS heterogeneity. Heterogeneous stiffness was defined when the first and second most predominant stages were more than one category apart. MLS values by each method were compared using the Wilcoxon signed-rank test. RESULTS: We included 128 patients with suspected liver fibrosis (mean age 54.4 ± 14.8 years). MLS was 2.7 ± 1.0 kPa for ROI measurements and 2.6 ± 0.9 kPa for the volumetric method (p = 0.001). Of 59 patients with normal stage (F0), 31 patients (52.5%) had > 20% of liver volume with abnormal LS (F1-F4). Heterogeneous LS was reported in 18 patients (14%). CONCLUSIONS: MLS measurement may not represent the entire spectrum of hepatic fibrosis. Volumetric segmentation may potentially improve the detection of heterogeneous fibrosis and the accuracy of LS measurement. KEY POINTS: • Heterogeneity of hepatic fibrosis may occur in patients with chronic liver disease. • MR elastography is used to assess hepatic fibrosis by measuring liver stiffness. • Measuring liver stiffness by the ROI method and reporting a mean value may fail to detect heterogeneity of hepatic fibrosis. Volumetric assessment of liver stiffness by MR elastography may detect heterogeneity of parenchymal involvement.

Follow-up of Incidentally Detected Pancreatic Cystic Neoplasms: Do Baseline MRI and CT Features Predict Cyst Growth?

Background Incidental detection of pancreatic cystic neoplasm (PCN) has increased. Since a small percentage of PCNs possess malignant potential, management is challenging. The recently revised American College of Radiology (ACR) recommendations define PCN measurement and growth for different categories based on baseline cyst size. However, no data are available regarding PCN growth rate under the ACR-defined size categories. Purpose To assess growth of incidentally detected PCNs on long-term imaging follow-up using revised ACR recommendations and to evaluate the association between baseline imaging features and growth. Materials and Methods This retrospective study included PCNs with baseline imaging performed between January 2002 and May 2017, with two or more cross-sectional imaging studies performed at least 12 months apart. PCN assessment was based on ACR 2017 recommendations. Cyst features, including location, septations, and mural nodules and multiplicity, were noted. Time to cyst progression (growth by ACR criteria) was examined by using baseline PCN size, among other factors. Results A total of 646 cysts in 390 patients were followed up for a median of 50 months (range, 12-186 months). A total of 184 (28.5%) cysts increased in size, 52 (8.1%) decreased in size, and 410 (63.4%) remained stable. For groups in which baseline PCN size was smaller than 5 mm, 5-14 mm, 15-25 mm, and larger than 25 mm, growth was noted in seven (13.2%), 106 (28.9%), 49 (32.2%), and 22 (29.7%) cysts, respectively. ACR baseline size categories (subhazard ratio: 2.8 [5-14-mm PCN group], 3.4 [15-25-mm PCN group], and 2.7 [>25 mm group], as compared with the <5 mm PCN group; P < .05 for each) demonstrated association with growth. Presence of mural nodules, septations, or lesion multiplicity failed to demonstrate association with growth. Among PCNs smaller than 5 mm at baseline, 100% of PCNs at 3-year follow-up and 94.2% of PCNs at 5-year follow-up were likely to remain stable. Conclusion American College of Radiology baseline size category of 15-25-mm pancreatic cystic neoplasms (PCNs) demonstrated the highest (3.1 times) likelihood of growth, as compared with the category of PCNs smaller than 5 mm. PCNs smaller than 5 mm at baseline did not demonstrate growth at 3-year imaging follow-up. © RSNA, 2019 Online supplemental material is available for this article.

Semi-quantitative visual assessment of hepatic tumor burden can reliably predict survival in neuroendocrine liver metastases treated with transarterial chemoembolization.

OBJECTIVES: To evaluate the accuracy and reproducibility of semi-quantitative visual assessment of hepatic tumor burden (HTB) on MRI and to investigate its prognostic value in predicting overall survival (OS) in neuroendocrine liver metastases (NELMs) treated with transarterial chemoembolization (TACE). METHODS: Three independent readers blinded to the quantitative HTB measurement reviewed baseline MRI in 111 NELM patients treated with TACE. Readers visually assessed and semi-quantitatively categorized HTB using the European Neuroendocrine Tumor Society (ENETS) guidelines. Quantitative HTB measured by manual segmentation was used as the reference standard. Agreements between quantitative and semi-quantitative measurement of HTB, as well as intra- and inter-reader reproducibility, were evaluated using weighted kappa coefficient and intraclass correlation coefficient (ICC). Survival analysis included the Kaplan-Meier curves and Cox regression. Harrell C-index was calculated to evaluate the prognostic value of semi-quantitative HTB for predicting OS. RESULTS: According to quantitative HTB, 41, 29, 25, and 16 patients were categorized into ≤ 10%, 11-25%, 26-50%, and > 50% groups, respectively. Agreements between quantitative and semi-quantitative measurement of HTB by each reader (weighted kappa, 0.82-0.96), intra-reader agreement (weighted kappa, 0.95), and inter-reader agreements (weighted kappa, 0.84-0.91; ICC, 0.98) were at least substantial to almost perfect. Semi-quantitative HTB was an independent prognostic factor in NELMs treated with TACE (multivariate Cox regression, p < 0.001), with prognostic value comparable to that of quantitative HTB (Harrell C-index, 0.735 for both semi-quantitative and quantitative HTB in multivariate regression). CONCLUSION: Semi-quantitative visual assessment of HTB using MRI is accurate and reproducible and could reliably predict OS in NELMs treated with TACE. KEY POINTS: • Semi-quantitative visual assessment of HTB using MR imaging is considerably accurate, reproducible, and efficient. • Visually assessed semi-quantitative HTB serves as an independent predictor of OS in NELMs treated with TACE.

Prognostic value of baseline volumetric multiparametric MR imaging in neuroendocrine liver metastases treated with transarterial chemoembolization.

OBJECTIVES: To determine whether baseline multiparametric MR imaging can predict overall survival (OS) and hepatic progression-free survival (HPFS) in patients with neuroendocrine liver metastases (NELMs) treated with transarterial chemoembolization (TACE). METHODS: This retrospective study included 84 NELMs patients treated with TACE. Tumor volume and volumetric measurements of arterial enhancement (AE), venous enhancement (VE), and apparent diffusion coefficient (ADC) were performed on baseline MR imaging. A maximum of one, two, and five index lesions were selected in each patient. OS was the primary endpoint and HPFS was the secondary endpoint. Prognostic values of volumetric multiparametric MR parameters for predicting OS and HPFS considering a maximum of one, two, and five index lesions were assessed. RESULTS: Prognostic values of volumetric multiparametric MR parameters for predicting OS and HPFS were similar regardless of the maximum number of index lesions. Multivariate survival analysis showed that baseline dominant tumor volume ≥ 73 cm3, volumetric mean AE ≥ 45%, and mean VE ≥ 73% were independent prognostic factors for OS (HR 2.73; 95% CI 1.45, 5.15; HR 0.32; 95% CI 0.17, 0.63; HR 0.35; 95% CI 0.17, 0.72, respectively) and HPFS (HR 2.30, 95% CI 1.38, 3.84; HR 0.46, 95% CI 0.25, 0.84; HR 0.36, 95% CI 0.19, 0.57, respectively). OS and HPFS were similar in patients with low and high volumetric mean ADC. CONCLUSION: Volumetric enhancement values and tumor volume of the dominant lesion on baseline MR imaging may act as prognostic factors for OS and HPFS in NELMs patients treated with TACE. KEY POINTS: • High volumetric mean AE and VE, and low tumor volume of the dominant lesion on baseline MR imaging were associated with favorable OS and HPFS in NELMs patients treated with TACE. • Evaluation of multiple lesions does not provide additional information as compared to single lesion evaluation.

Added value of apparent diffusion coefficient in distinguishing between serous and mucin-producing pancreatic cystic neoplasms.

OBJECTIVES: To evaluate the added value of diffusion-weighted imaging (DWI) on MRI in differentiating serous from mucin-producing pancreatic cystic neoplasms (PCNs). METHODS: One hundred seventeen patients with PCN measuring ≥ 10 mm were included. Three readers independently evaluated MRI with and without the use of apparent diffusion coefficient (ADC). Logistic regression was used to analyze whether confidence scores were different with the use of different image sets. Diagnostic performance with and without ADC was compared. RESULTS: DWI/ADC improved confidence in 44.8%, 73.6%, and 78.2% of patients by the three readers in distinguishing serous from mucin-producing PCNs. The use of ADC increased the probability of a higher confidence in the differentiation as compared to morphological imaging for all three readers (p < 0.001). Odds ratio for increase in the diagnostic confidence with the use of ADC for the three readers with decreasing years of experience were 5.8, 6.8, and 12.7. The diagnostic accuracy of morphological MRI with ADC was higher than that without ADC for two of three readers with lesser experience (87.2% vs. 80.8%; 91.5% vs. 80.8%). CONCLUSION: DWI may have added value as a complementary tool to conventional morphological MRI in differentiating between serous and mucin-producing PCNs with possibly greater value for readers with less experience in reading abdominal MRI. KEY POINTS: • Optimal management of PCNs requires differentiation of serous from mucin-producing PCNs. • ADC measurements allow increased confidence in differentiating serous from mucin-producing PCNs. • ADC measurements increase the accuracy in diagnosing serous versus mucin-producing PCNs.

Baseline Volumetric Multiparametric MRI: Can It Be Used to Predict Survival in Patients with Unresectable Intrahepatic Cholangiocarcinoma Undergoing Transcatheter Arterial Chemoembolization?

Purpose To evaluate whether baseline MRI can help predict survival in patients with unresectable intrahepatic cholangiocarcinoma (ICCA) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. The study included 111 patients (mean age, 62 years ± 12; range, 29-86 years), with 44 men (mean age, 61 years ± 12; range, 29-81 years) and 67 women (mean age, 63 years ± 12; range, 34-86 years). Patients underwent TACE after baseline MRI, which included contrast-enhanced and diffusion-weighted imaging with apparent diffusion coefficient (ADC) mapping between 2003 and 2016. The single largest tumor was assessed independently by a radiologist for anatomic and functional (viable tumor volume, percentage viable tumor volume [100 × viable tumor volume/whole tumor volume], viable tumor burden [100 × viable tumor volume/whole liver volume], and ADC) parameters. Survival analysis was performed with Kaplan-Meier and Cox regression analysis. Results Overall survival (OS) was higher with a baseline ADC of 1415 × 10-6 mm2/sec or less compared with greater than 1415 × 10-6 mm2/sec (P = .005; 25th percentile of OS, 17 months vs 7 months, respectively), percentage viable tumor volume greater than 90% compared with 90% or less (P = .001; 25th percentile of OS, 20 months vs 7 months, respectively), and viable tumor burden greater than 6.6% compared with 6.6% or less (P = .09; 25th percentile of OS, 17 months vs 7 months, respectively). Baseline ADC greater than 1415 × 10-6 mm2/sec (hazard ratio [HR]: 2.176 [95% confidence interval: 1.217, 3.891]; P = .009) and percentage viable tumor volume greater than 90% (HR: 0.319 [95% confidence interval: 0.148, 0.685]; P = .003) were associated with OS independent of clinical confounders (age and sex). At multiparametric MRI risk stratification (with low ADC and high percentage viable tumor volume considered favorable for survival), differences in OS were noted (P = .002; 25th percentile of OS for low vs intermediate vs high risk, 22 months vs 10 months vs 7 months, respectively). Conclusion Baseline multiparametric MRI assessment including volumetric ADC, percentage viable tumor volume, and viable tumor burden can help predict mortality risk among patients with intrahepatic cholangiocarcinoma undergoing transcatheter arterial chemoembolization. © RSNA, 2018 Online supplemental material is available for this article.

Unresectable Intrahepatic Cholangiocarcinoma: Multiparametric MR Imaging to Predict Patient Survival.

Purpose To determine the performance of magnetic resonance (MR) imaging-based tumor metrics for evaluation of response to transarterial chemoembolization (TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICCA). Materials and Methods Ninety-four patients with unresectable ICCA underwent baseline and follow-up MR imaging after TACE and were followed up until death or end of study duration. Lesions were analyzed for anatomic (Response Evaluation Criteria in Solid Tumors [RECIST] and tumor volume) and functional (viable tumor volume, viable tumor burden, and apparent diffusion coefficient [ADC]) volumetric MR parameters by using semiautomatic software. Response was assessed by using changes in viable tumor volume by using modified RECIST (mRECIST)-derived thresholds (three-dimensional mRECIST), viable tumor burden, and ADC. Overall survival was the primary endpoint. Cox-regression and Kaplan-Meier survival analysis were used. Results Tumor volume did not change after TACE (P = .07) whereas RECIST diameter showed a small change (-2.6%; P = .02). There was an increase in ADC (20.7%) and a decrease in viable tumor volume (-29.3%) and viable tumor burden (-29.1%; P < .001 for all). Higher overall survival was noted among responders by using thresholds of 25% increase in ADC, 66% decrease in viable tumor volume, and 50% decrease in viable tumor burden (log-rank test, P < .05). Hazard ratio for nonresponders by using ADC, three-dimensional mRECIST, and viable tumor burden at multivariable analysis was 2.9 (P = .004), 4.1 (P = .009), and 4.0 (P = .002), respectively. Survival differences were noted for patients who showed response by using all three parameters (ADC, three-dimensional mRECIST, and viable tumor burden) versus those who showed response by using either one or two of these parameters versus those who showed no response (P < .001). Conclusion Changes in volumetric ADC, viable tumor volume, and viable tumor burden at MR imaging provide prognostic information among patients with unresectable ICCA who undergo TACE. © RSNA, 2018 Online supplemental material is available for this article.

Utility of volumetric contrast-enhanced and diffusion-weighted MRI in differentiating between common primary hypervascular liver tumors.

BACKGROUND: Differentiating between hepatocellular carcinoma (HCC), focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) is usually achievable by MRI. However, in some cases with atypical imaging findings accurate diagnosis may be difficult. PURPOSE: To assess the diagnostic value of volumetric contrast-enhanced (CE) and volumetric diffusion-weighted imaging (DWI) in differentiating between HCC, FNH, and HCA. STUDY TYPE: Retrospective. SUBJECTS: In all, 143 patients (206 lesions): 42 HCA (81 lesions), 51 FNH (65 lesions), and 50 HCC (60 lesions). FIELD STRENGTH/SEQUENCE: 1.5T MRI, T1 -T2 WI, DWI. ASSESSMENT: Patients underwent CE-MRI and DWI (b = 0, 750 mm2 /s). Volumetric assessment of lesions' contrast enhancement and apparent diffusion coefficient (ADC) was performed with semiautomatic software after 3D image registration and segmentation by an observer and compared between three lesion groups. The diagnosis of lesions was based on histopathology, typical MRI findings, and/or follow-up. STATISTICAL TESTS: Independent t-test was used to compare parameters between two groups, one-way analysis of variance (ANOVA) between three groups, and receiver operator characteristic curve (ROC) analysis to define under-curve area and optimal cutoff. RESULTS: Mean values (±standard deviation) for HCC, FNH, and HCA, respectively, were: 1) arterial enhancement (%), 40.5 ± 13.2, 88.6 ± 32.6, 69.6 ± 25.1; 2) venous enhancement (%) 72.4 ± 22.1, 95.2 ± 30.9, 80.7 ± 30.6; and 3) ADC (10-6 mm2 /s) 1404.5 ± 168.1, 1413.4 ± 232.1, 1070.1 ± 232.1. ADC was the best differentiator of HCA from FNH (at 1211 × 10-6 mm2 /s; sensitivity 80.4%, specificity 71.7%) and arterial enhancement was the best differentiator of HCC from both HCA (at 48%; sensitivity 80.0%, specificity 80.5%) and FNH (at 52%; sensitivity 85.7%, specificity 85.4%). A combination of arterial enhancement and ADC (at 50% and 1227 × 10-6 mm2 /s) differentiated three types of tumors with high specificity (87.9%). DATA CONCLUSION: Volumetric CE-MRI and volumetric DWI can help to differentiate between HCC, FNH, and HCA. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1080-1090.

Prediction of post-TACE necrosis of hepatocellular carcinoma usingvolumetric enhancement on MRI and volumetric oil deposition on CT, with pathological correlation.

OBJECTIVE: To investigate whether volumetric enhancement on baseline MRI and volumetric oil deposition on unenhanced CT would predict HCC necrosis and response post-TACE. METHOD: Of 115 retrospective HCC patients (173 lesions) who underwent cTACE, a subset of 53 HCC patients underwent liver transplant (LT). Semiautomatic volumetric segmentation of target lesions was performed on dual imaging to assess the accuracy of predicting tumour necrosis after TACE in the whole cohort and at pathology in the LT group. Predicted percentage tumour necrosis is defined as 100 % - (%baseline MRI enhancement - %CT oil deposition). RESULTS: Mean predicted tumour necrosis by dual imaging modalities was 61.5 % ± 31.6%; mean percentage tumour necrosis on follow-up MRI was 63.8 % ± 31.5 %. In the LT group, mean predicted tumour necrosis by dual imaging modalities was 77.6 % ± 27.2 %; mean percentage necrosis at pathology was 78.7 % ± 31.5 %. There was a strong significant correlation between predicted tumour necrosis and volumetric necrosis on MRI follow-up (r = 0.889, p<0.001) and between predicted tumour necrosis and pathological necrosis (r = 0.871, p<0.001). CONCLUSION: Volumetric pre-TACE enhancement on MRI and post-TACE oil deposition in CT may accurately predict necrosis in treated HCC lesions. KEY POINTS: • Imaging-based tumour response can assist in therapeutic decisions. • Lipiodol retention as carrier agent in cTACE is a tumour necrosis biomarker. • Predicting tumour necrosis with dual imaging potentially obviates immediate post-treatment MRI. • Predicting tumour necrosis would facilitate further therapeutic decisions in HCC post-cTACE. • Pre-TACE MRI and post-TACE CT predict necrosis in treated HCC.

Are pancreatic IPMN volumes measured on MRI images more reproducible than diameters? An assessment in a large single-institution cohort.

OBJECTIVES: To assess reproducibility of volume and diameter measurement of intraductal papillary mucinous neoplasms (IPMNs) on MRI images. METHODS: Three readers measured the diameters and volumes of 164 IPMNs on axial T2-weighted images and coronal thin-slice navigator heavily T2-weighted images using manual and semiautomatic techniques. Interobserver reproducibility and variability were assessed. RESULTS: Interobserver intraclass correlation coefficients (ICCs) for the largest diameter measured using manual and semiautomatic techniques were 0.979 and 0.909 in the axial plane, and 0.969 and 0.961 in the coronal plane, respectively. Interobserver ICCs for the volume measurements were 0.973 and 0.970 in axial and coronal planes, respectively. The highest intraobserver reproducibility was noted for coronal manual measurements (ICC 0.981) followed by axial manual measurements (ICC 0.969). For the diameter measurements, Bland-Altman analysis revealed the lowest interobserver variability for manual axial measurements with an average range of 95% limits of agreement (LOA) of 0.68 cm. Axial and coronal volume measurements showed similar 95% LOA ranges (8.9 cm3 and 9.4 cm3, respectively). CONCLUSIONS: Volume and diameter measurements on axial and coronal images show good interobserver and intraobserver reproducibility. The single largest diameter measured manually on axial images showed the highest reproducibility and lowest variability. The 95% LOA may help define reproducible size changes in these lesions using measurements from different readers. KEY POINTS: • MRI measurements by different radiologists can be used for IPMN follow-up. • Both diameter and volume measurements demonstrate excellent interobserver and intraobserver reproducibility. • Manual axial measurements show the highest interobserver reproducibility in determining size. • Axial and coronal volume measurements show similar limits of agreement. • Manual axial measurements show the lowest variability in agreement range.

Accuracy of apparent diffusion coefficient in differentiating pancreatic neuroendocrine tumour from intrapancreatic accessory spleen.

OBJECTIVES: To evaluate and compare the accuracy of absolute apparent diffusion coefficient (ADC) and normalised ADC (lesion-to-spleen ADC ratio) in differentiating pancreatic neuroendocrine tumour (NET) from intrapancreatic accessory spleen (IPAS). METHODS: Study included 62 patients with the diagnosis of pancreatic NET (n=51) or IPAS (n=11). Two independent reviewers measured ADC on all lesions and spleen. Receiver operating characteristics (ROC) analysis to differentiate NET from IPAS was performed and compared for absolute and normalised ADC. Inter-reader reliability for the two methods was assessed. RESULTS: Pancreatic NET had significantly higher absolute ADC (1.431x10-3 vs 0.967x10-3 mm2/s; P<0.0001) and normalised ADC (1.59 vs 1.09; P<0.0001) compared to IPAS. An ADC value of ≥1.206x10-3 mm2/s was 70.6% sensitive and 90.9% specific for the diagnosis of NET vs. IPAS. Lesion to spleen ADC ratio of ≥1.25 was 80.4% sensitive, and 81.8% specific while ratio of ≥1.29 was 74.5% sensitive and 100% specific in the differentiation. The area under the curve (AUCs) for two methods were similar (88.2% vs. 88.8%; P=0.899). Both methods demonstrated excellent inter-reader reliability with ICCs for absolute ADC and ADC ratio being 0.957 and 0.927, respectively. CONCLUSION: Both absolute and normalised ADC allow clinically relevant differentiation of pancreatic NET and IPAS. KEY POINTS: • Imaging overlaps between IPASs and pancreatic-NETs lead to unnecessary procedures including pancreatectomy. • Uniquely low ADC of spleen allows differentiating IPASs from pancreatic NETs. • Both absolute-ADC and normalised-ADC (lesion-to-spleen ADC-ratio) demonstrate high accuracy in differentiating IPASs from NETs. • Both methods demonstrate excellent inter-reader reliability.

Long-term stability in biomass and production of terpene indole alkaloids by hairy root culture of Rauvolfia serpentina and cost approximation to endorse commercial realism.

The effect of 6 years of cultivation and use of table-sugar (TS) on the biomass/terpene alkaloid productivities and rol gene expression were studied in a hairy root (HR) clone of Rauvolfia serpentina. The media cost could be reduced >94 % by replacing sucrose (SUC) with TS­an unexplored avenue for HR cultivation. The overall productivities increased over long-term cultivation with sugar proving superior to SUC for biomass (24.4 ± 2.11 g/l DW after 40 days to 17.31 % higher) and reserpine (0.094 ± 0.008 % DW after 60 days to 193.8 % more) production. The latter however revealed comparatively better yields concerning ajmaline (0.507 ± 0.048 % DW after 60 days to 61.98 % higher) and yohimbine (0.628 ± 0.062 % DW after 60 days to 38.32 % higher), respectively. PCR amplification of rol genes confirmed long-term expression stability.

Incremental value of volumetric multiparametric MRI over Fudan score for prognosis of unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy.

BACKGROUND: Individualized patient care requires prognostic models customized to a tumor and an individual's disease profile for reliable survival prediction. MRI has prognostic value for intrahepatic cholangiocarcinoma (ICCA). Existing prognostic models for ICCA exclude imaging-based information about an individual's tumor that may reflect important aspects of tumor's biology. Fudan score, a prognostic model applicable to unresectable ICCA, is limited by subjective morphologic imaging parameters. OBJECTIVES: To assess the prognostic value of baseline volumetric multiparametric MRI in unresectable intrahepatic cholangiocarcinoma (ICCA) treated with systemic chemotherapy and the incremental value of MRI over the Fudan score. METHODS: This retrospective study included 114 ICCA patients treated with systemic chemotherapy between 2007 and 2021 after a baseline MRI. The single largest tumor was volumetrically assessed for anatomic (total tumor volume and diameter) and functional parameters (viable tumor volume, percentage-viable tumor volume, viable tumor burden, and ADC). A derivation cohort of 30 patients was utilized to identify MRI parameters associated with overall survival (OS) using Cox regression analysis. The incremental value of MRI over Fudan score was assessed on an independent sub-cohort of 84 patients using Kaplan-Meier analysis and C-index. RESULTS: 114 patients (64 years +/- 11; 61 women) were evaluated. Pre-treatment high (>1350x10-6 mm2/sec) ADC was the only independent predictor of OS (HR, 8.07; P < 0.001). Replacing subjective tumor boundary with objective ADC value, and using modified biochemical thresholds increased the prognostic stratification for the risk groups in the modified ADC-Fudan model compared to the original Fudan model (median survival 12 and 4.5 months; P = 0.055; vs. 11 and 3 months; P < 0.001). The modified ADC-Fudan model demonstrated an 11 % improvement over the original Fudan model (c-index: 0.80 vs. 0.69; P = 0.044) for survival prediction. CONCLUSIONS: High pre-treatment volumetric ADC was associated with unfavorable prognosis in patients with unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy. Supplementing the original Fudan model with ADC and modified serum marker thresholds improved the survival prediction performance by 11% in the resulting modified ADC-Fudan model. CLINICAL IMPACT: Volumetric MRI could improve the survival prediction among ICCA patients prior to receiving potentially toxic and expensive palliative chemotherapies. This could potentially guide individualized therapy for this patient cohort.

Facility assessment of the best functioning facility providing emergency obstetric care in the selected blocks of Varanasi, Uttar Pradesh.

Background: UP has the 2nd highest MMR which is 197 compared with national average of 113 (RGI-SRS-2016-2018).Although institutional deliveries in India has been increased from 78.9% (NFHS-4) to 89% (NFHS-5) [ UP from 67.8% to 83.4%] but still we are far away from SDG -3 target. It reflects that there may be increase in crude coverage but not in effective coverage. Materials and Methods: It is a cross sectional study conducted in May - June 2017. Out of 8 blocks of rural Varanasi, 4 blocks were selected randomly. Best functioning facility for EmOC services in each selected block were assessed using Facility Gap Assessment Schedule of IPHS. Result: None of the facility met the recommended standard for BEmOC .Tracking of drop out of ANC and PNC services, use of Partograph, treatment of abortion-related complications, were not found at all the 4 facility. Blood grouping and RH typing was also not functional at 2 of the 4 centers. Caesarean section and availability of blood bank were also lacking in CHC (FRU). Conclusion: If condition of best functioning facility in a block is not according to the recommendation then how can we expect to provide a good maternal health service to public.