Diffusion kurtosis imaging-derived histogram metrics for prediction of KRAS mutation in rectal adenocarcinoma: Preliminary findings.

BACKGROUND: Although histological examination is the standard method for assessing genetic status, the development of a noninvasive method, which can display the heterogeneity of the whole tumor to supplement genotype analysis, might be important for personalized treatment strategies. PURPOSE: To evaluate the potential role of diffusion kurtosis imaging (DKI)-derived parameters using histogram analysis derived from whole-tumor volumes for prediction of the status of KRAS mutations in patients with rectal adenocarcinoma. STUDY TYPE: Retrospective. SUBJECTS: In all, 148 consecutive patients with histologically confirmed rectal adenocarcinoma who were treated at our institution. SEQUENCE: DKI was performed with a 3.0 T MRI system using a single-shot echo-planar imaging sequence with b values of 0, 700, 1400, and 2100 sec/mm2 . ASSESSMENT: D, K, and apparent diffusion coefficient (ADC) values were measured using whole-tumor volume histogram analysis and were compared between different KRAS mutations status. STATISTICAL TESTS: Student's t-test or Mann-Whitney U-test, and receiver operating characteristic (ROC) curves were used for statistical analysis. RESULTS: All the percentile metrics of ADC and D values were significantly lower in the mutated group than those in the wildtype group (all P < 0.05), except for the minimum value of ADC and D (both P > 0.05), while K-related percentile metrics were higher in the mutated group compared with those in the wildtype group (all P < 0.05). Regarding the comparison of the diagnostic performance of all the histogram metrics, K75th showed the highest AUC value of 0.871, and the corresponding values for sensitivity, specificity, positive predictive value, and negative predictive value were 81.43%, 78.21%, 77.03%, and 82.43%, respectively. DATA CONCLUSION: DKI metrics with whole-tumor volume histogram analysis is associated with KRAS mutations, and thus may be useful for predicting the KRAS status of rectal cancers for guiding targeted therapy. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:930-939.

Radiomics analysis of multiparametric MRI for prediction of pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVES: To develop and validate a radiomics predictive model based on pre-treatment multiparameter magnetic resonance imaging (MRI) features and clinical features to predict a pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after receiving neoadjuvant chemoradiotherapy (CRT). METHODS: One hundred and eighty-six consecutive patients with LARC (training dataset, n = 131; validation dataset, n = 55) were enrolled in our retrospective study. A total of 1,188 imaging features were extracted from pre-CRT T2-weighted (T2-w), contrast-enhanced T1-weighted (cT1-w) and ADC images for each patient. Three steps including least absolute shrinkage and selection operator (LASSO) regression were performed to select key features and build a radiomics signature. Combining clinical risk factors, a radiomics nomogram was constructed. The predictive performance was evaluated by receiver operator characteristic (ROC) curve analysis, and then assessed with respect to its calibration, discrimination and clinical usefulness. RESULTS: Thirty-one of 186 patients (16.7%) achieved pCR. The radiomics signature derived from joint T2-w, ADC, and cT1-w images, comprising 12 selected features, was significantly associated with pCR status and showed better predictive performance than signatures derived from either of them alone in both datasets. The radiomics nomogram, incorporating the radiomics signature and MR-reported T-stages, also showed good discrimination, with areas under the ROC curves (AUCs) of 0.948 (95% CI, 0.907-0.989) and 0.966 (95% CI, 0.924-1.000), as well as good calibration in both datasets. Decision curve analysis confirmed its clinical usefulness. CONCLUSIONS: This study demonstrated that the pre-treatment radiomics nomogram can predict pCR in patients with LARC and potentially guide treatments to select patients for a "wait-and-see" policy. KEY POINTS: • Radiomics analysis of pre-CRT multiparameter MR images could predict pCR in patients with LARC. • Proposed radiomics signature from joint T2-w, ADC and cT1-w images showed better predictive performance than individual signatures. • Most of the clinical characteristics were unable to predict pCR.

Whole-tumour diffusion kurtosis MR imaging histogram analysis of rectal adenocarcinoma: Correlation with clinical pathologic prognostic factors.

OBJECTIVE: To investigate potential relationships between diffusion kurtosis imaging (DKI)-derived parameters using whole-tumour volume histogram analysis and clinicopathological prognostic factors in patients with rectal adenocarcinoma. MATERIAL AND METHODS: 79 consecutive patients who underwent MRI examination with rectal adenocarcinoma were retrospectively evaluated. Parameters D, K and conventional ADC were measured using whole-tumour volume histogram analysis. Student's t-test or Mann-Whitney U-test, receiver operating characteristic curves and Spearman's correlation were used for statistical analysis. RESULTS: Almost all the percentile metrics of K were correlated positively with nodal involvement, higher histological grades, the presence of lymphangiovascular invasion (LVI) and circumferential margin (CRM) (p<0.05), with the exception of between K10th, K90th and histological grades. In contrast, significant negative correlations were observed between 25th, 50th percentiles and mean values of ADC and D, as well as ADC10th, with tumour T stages (p< 0.05). Meanwhile, lower 75th and 90th percentiles of ADC and D values were also correlated inversely with nodal involvement (p< 0.05). Kmean showed a relatively higher area under the curve (AUC) and higher specificity than other percentiles for differentiation of lesions with nodal involvement. CONCLUSION: DKI metrics with whole-tumour volume histogram analysis, especially K parameters, were associated with important prognostic factors of rectal cancer. KEY POINTS: • K correlated positively with some important prognostic factors of rectal cancer. • K mean showed higher AUC and specificity for differentiation of nodal involvement. • DKI metrics with whole-tumour volume histogram analysis depicted tumour heterogeneity.

Preparation and pharmacokinetics in vivo of linarin solid dispersion and liposome.

Objective: The current investigation aimed to determine the appropriate dosage form by comparing solid dispersion and liposome to achieve the purpose of improving the solubility and bioavailability of linarin. Methods: Linarin solid dispersion (LSD) and linarin liposome (LL) were developed via the solvent method and the thin film hydration method respectively. The Transwell chamber model of Caco-2 cells was established to evaluate the absorption of drug. The pharmacokinetics of linarin, LSD and LL in rats after ig administration were carried out by high performance liquid chromatography (HPLC) method. Results: The solubility of LSD and LL was severally 3.29 times and 3.09 times than that of linarin. The permeation coefficients of LSD and LL were greater than 10-6, indicating that the absorption of LSD and LL were both better than linarin. The bioavailability of the LSD was 3.363 times higher than that of linarin, and the bioavailability of LL was 0.9886 times higher than that of linarin. Conclusion: The linarin was more suitable for making solid dispersion to enhance its solubility and bioavailability.

Preparation of Benzyl Quinine-modified Monolithic Column for Reversed-phase Capillary Electrochromatography.

N-Benzylquininium chloride is a versatile functional monomer with quinoline and benzyl groups, which is beneficial for reversed-phase chromatography. In this study, a novel monolithic column with reversed-phase mode was synthesized using N-benzylquininium chloride as the monomer and 3-(acryloyloxy)-2-hydroxypropyl methacrylate as the cross-linker in a binary porogenic solvent consisting of PEG 400 and a 0.05 M sodium hydroxide aqueous solution. The alkaline solution were found to be useful for the improvement of the mechanical stability of the porous monoliths. The monolithic column showed excellent reversed-phase selectivity and various compounds, such as alkylbenzenes, phenols and polycyclic aromatic hydrocarbons, were separated successfully. The highest column efficiency was 1.75 × 105 N m-1. The relative standard deviations of the migration time for thiourea and four alkylbenzenes were all less than 5.0%, which indicates the monolithic column has good stability. The application of the monolithic column for the analysis of polycyclic aromatic hydrocarbons in spiked lake water samples illustrated its great potential for practical application.