MRI-derived radiomics analysis improves the noninvasive pretreatment identification of multimodality therapy candidates with early-stage cervical cancer.

OBJECTIVES: To develop and validate a clinical-radiomics model that incorporates radiomics signatures and pretreatment clinicopathological parameters to identify multimodality therapy candidates among patients with early-stage cervical cancer. METHODS: Between January 2017 and February 2021, 235 patients with IB1-IIA1 cervical cancer who underwent radical hysterectomy were enrolled and divided into training (n = 194, training:validation = 8:2) and testing (n = 41) sets according to surgical time. The radiomics features of each patient were extracted from preoperative sagittal T2-weighted images. Significance testing, Pearson correlation analysis, and Least Absolute Shrinkage and Selection Operator were used to select radiomic features associated with multimodality therapy administration. A clinical-radiomics model incorporating radiomics signature, age, 2018 Federation International of Gynecology and Obstetrics (FIGO) stage, menopausal status, and preoperative biopsy histological type was developed to identify multimodality therapy candidates. A clinical model and a clinical-conventional radiological model were also constructed. A nomogram and decision curve analysis were developed to facilitate clinical application. RESULTS: The clinical-radiomics model showed good predictive performance, with an area under the curve, sensitivity, and specificity in the testing set of 0.885 (95% confidence interval: 0.781-0.989), 78.9%, and 81.8%, respectively. The AUC, sensitivity, and specificity of the clinical model and clinical-conventional radiological model were 0.751 (0.603-0.900), 63.2%, and 63.6%, 0.801 (0.661-0.942), 73.7%, and 68.2%, respectively. A decision curve analysis demonstrated that when the threshold probability was > 20%, the clinical-radiomics model or nomogram may be more advantageous than the treat all or treat-none strategy. CONCLUSIONS: The clinical-radiomics model and nomogram can potentially identify multimodality therapy candidates in patients with early-stage cervical cancer. KEY POINTS: • Pretreatment identification of multimodality therapy candidates among patients with early-stage cervical cancer helped to select the optimal primary treatment and reduce severe complication risk and costs. • The clinical-radiomics model achieved a better prediction performance compared with the clinical model and the clinical-conventional radiological model. • An easy-to-use nomogram exhibited good performance for individual preoperative prediction.

Assessment of Changes in the Cesarean Scar and Uterus Between One and Two Years after Cesarean Section Using 3D T2w SPACE MRI.

Objective To evaluate changes in morphology of the cesarean scar and uterus between one and two years after cesarean section using high-resolution, three dimensional T2-weighted sampling perfection with application optimized contrast using different flip angle evolutions Magnetic Resonance Imaging (3D T2w SPACE MRI). Methods This prospective study was performed to investigate morphological changes in the cesarean scars and uterus from one to two years after cesarean section using high-resolution, 3D T2w SPACE MRI. The healthy volunteers having no childbearing history were recruited as the controls. All data were measured by two experienced radiologists. All data with normal distribution between the one-year and two-year groups were compared using a paired-sample t test or independent t test. Results Finally, 46 women took a pelvic MR examination one year after cesarean section, and a subset of 15 completed the same examination again after two years of cesarean section. Both the uterine length and the anterior wall thickness after two years of cesarean section (5.75 ± 0.46 and 1.45 ± 0.35 cm) were significantly greater than those measured at one year (5.33 ± 0.59 and 1.25 ± 0.27 cm) (t = -2.363 and -2.175, P= 0.033 and 0.048). No significant difference was shown in myometrial thickness two years after cesarean section (1.45 ±0.35 cm) with respect to the control group (1.58 ± 0.21 cm, P= 0.170). Nine women who underwent MRI twice were considered to have scar diverticula one year after cesarean section, and still had diverticula two years after cesarean section. The thickness, height, and width of the uterine scar showed no significant change from one to two years (all P > 0.05). Conclusions 3D T2w SPACE MRI provides overall morphologic details and shows dynamic changes in the scar and the uterus between one and two years after cesarean section. Scar morphology after cesarean section reached relatively stable one year after cesarean section, and uterine morphology was closer to normal two years after cesarean section.

Three-dimensional MR Elastography Depicts Liver Inflammation, Fibrosis, and Portal Hypertension in Chronic Hepatitis B or C.

Background The value of measuring mechanical properties to categorize various pathophysiologic states of the liver is as yet undetermined in chronic hepatitis B (CHB) or C (CHC). Purpose To evaluate multiparametric three-dimensional (3D) MR elastography as a means of detecting early necroinflammation, distinguishing necroinflammation from fibrosis, and gauging the severity of portal hypertension (PH) in CHB or CHC. Materials and Methods From January 2015 to September 2019, participants with CHB or CHC were prospectively enrolled from a single institution and were divided into two groups: those with liver biopsy and no evidence of PH (group 1) and those with PH and a hepatic venous pressure gradient (HVPG) measurement (group 2). For group 3, healthy volunteers were separately recruited from a nearby community. Multiple viscoelastic parameters (shear stiffness [SS], storage modulus, loss modulus, and damping ratio [DR]) were determined at 3D MR elastography at 60 Hz, and multivariable logistic or linear regression analysis was used to assess associations of mechanical parameters with histologic scores and HVPG. Results A total of 155 participants (median age, 41 years [interquartile range, 32-48 years]; 85 women) were in group 1 (training set: n = 78, validation set: n = 77), 85 participants (median age, 57 years [interquartile range, 43-61 years]; 51 women) in group 2, and 60 healthy volunteers (median age, 49 years [interquartile range, 27-64 years]; 38 men) in group 3. The liver DR was higher in participants with necroinflammation (DR, 0.13 ± 0.03) versus those without (at liver fibrosis stage F0) (DR, 0.10 ± 0.02; P < .001). Liver DR and SS together performed well in the diagnosis of necroinflammation (area under the receiver operating characteristic curve [AUC], 0.88 [95% CI: 0.79, 0.96]) and the scoring of moderate to severe activity (AUC, 0.88 [95% CI: 0.81, 0.95]) in the validation data set. Liver DR (regression coefficient [ß] = -30.3 [95% CI: -58.0, -2.5]; P = .03) and splenic SS (ß = 2.3 [95% CI: 1.7, 2.9]; P < .001) were independently associated with HVPG. Conclusion Three-dimensional MR elastography may detect early necroinflammation, distinguish necroinflammation from liver fibrosis, and correlate with hepatic venous pressure gradient in chronic hepatitis B and C. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Reeder in this issue.

Radiomics Based on MRI as a Biomarker to Guide Therapy by Predicting Upgrading of Prostate Cancer From Biopsy to Radical Prostatectomy.

BACKGROUND: Biopsy Gleason score (GS) is crucial for prostate cancer (PCa) treatment decision-making. Upgrading in GS from biopsy to radical prostatectomy (RP) puts a proportion of patients at risk of undertreatment. PURPOSE: To develop and validate a radiomics model based on multiparametric magnetic resonance imaging (mp-MRI) to predict PCa upgrading. STUDY TYPE: Retrospective, radiomics. POPULATION: A total of 166 RP-confirmed PCa patients (training cohort, n = 116; validation cohort, n = 50) were included. FIELD STRENGTH/SEQUENCE: 3.0T/T2 -weighted (T2 W), apparent diffusion coefficient (ADC), and dynamic contrast enhancement (DCE) sequences. ASSESSMENT: PI-RADSv2 score for each tumor was recorded. Radiomic features were extracted from T2 W, ADC, and DCE sequences and Mutual Information Maximization criterion was used to identify the optimal features on each sequence. Multivariate logistic regression analysis was used to develop predictive models and a radiomics nomogram and their performance was evaluated. STATISTICAL TESTS: Student's t or chi-square were used to assess the differences in clinicopathologic data between the training and validation cohorts. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated. RESULTS: In PI-RADSv2 assessment, 67 lesions scored 5, 70 lesions scored 4, and 29 lesions scored 3. For each sequence, 4404 features were extracted and the top 20 best features were selected. The radiomics model incorporating signatures from the three sequences achieved better performance than any single sequence (AUC: radiomics model 0.868, T2 W 0.700, ADC 0.759, DCE 0.726). The combined mode incorporating radiomics signature, clinical stage, and time from biopsy to RP outperformed the clinical model and radiomics model (AUC: combined model 0.910, clinical model 0.646, radiomics model 0.868). The nomogram showed good performance (AUC 0.910) and calibration (P-values: training cohort 0.624, validation cohort 0.294). DATA CONCLUSION: Radiomics based on mp-MRI has potential to predict upgrading of PCa from biopsy to RP. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5 J. Magn. Reson. Imaging 2020;52:1239-1248.

CT radiomics nomogram for the preoperative prediction of lymph node metastasis in gastric cancer.

PURPOSE: To investigate the role of computed tomography (CT) radiomics for the preoperative prediction of lymph node (LN) metastasis in gastric cancer. MATERIALS AND METHODS: This retrospective study included 247 consecutive patients (training cohort, 197 patients; test cohort, 50 patients) with surgically proven gastric cancer. Dedicated radiomics prototype software was used to segment lesions on preoperative arterial phase (AP) CT images and extract features. A radiomics model was constructed to predict the LN metastasis by using a random forest (RF) algorithm. Finally, a nomogram was built incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were used to validate the capability of the radiomics model and nomogram on both the training and test cohorts. RESULTS: The radiomics model showed a favorable discriminatory ability in the training cohort with an area under the curve (AUC) of 0.844 (95% CI, 0.759 to 0.909), which was confirmed in the test cohort with an AUC of 0.837 (95% CI, 0.705 to 0.926). The nomogram consisted of radiomics scores and the CT-reported LN status showed excellent discrimination in the training and test cohorts with AUCs of 0.886 (95% CI, 0.808 to 0.941) and 0.881 (95% CI, 0.759 to 0.956), respectively. CONCLUSIONS: The CT-based radiomics nomogram holds promise for use as a noninvasive tool in the individual prediction of LN metastasis in gastric cancer. KEY POINTS: • CT radiomics showed a favorable performance for the prediction of LN metastasis in gastric cancer. • Radiomics model outperformed the routine CT in predicting LN metastasis in gastric cancer. • The radiomics nomogram holds potential in the individualized prediction of LN metastasis in gastric cancer.

Three-dimensional turbo-spin-echo amide proton transfer-weighted mri for cervical cancer: A preliminary study.

BACKGROUND: Amide proton transfer-weighted (APTw) imaging has shown great potential in the diagnosis of cancer, but has yet not been well studied in cervical cancer. PURPOSE: To evaluate the image quality and clinical feasibility of APTw MRI for cervical cancer. STUDY TYPE: Prospective. POPULATION: In all, 75 patients with cervical lesions and 49 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0 T, 3D turbo spin echo (TSE) APTw sequence. ASSESSMENT: Three radiologists, blinded to the clinical data, independently evaluated APTw image quality with a 5-point Likert scale on 64 patients with pathologically confirmed cervical cancer. APT values, calculated based on asymmetry of acquired Z-spectrum with respect to water frequency, using 3D turbo spin echo volume acquisition with B0 correction, were independently measured by two radiologists, twice for each observer, on 52 cervical cancer lesions and 49 normal cervical stroma with a mean region of interest area of 638.6 mm2 and 557.5 mm2 , respectively. STATISTICAL TESTS: Interobserver agreement was evaluated by Kendall's W test. Intra- and interobserver interclass correlation coefficients (ICC) were computed. Student's t-test was used to compare the differences of APT values between cervical cancer and normal cervix; receiver operating characteristic analysis was performed. RESULTS: Most cases revealed good APTw image quality with excellent agreement (Kendall's W = 0.850, P < 0.001). APT values of cervical cancer and normal cervical stroma were 2.745 ± 0.065 and 1.853 ± 0.059, respectively, with a significant difference (P < 0.0001). Intraobserver ICCs were 0.963 and 0.960 for two readers. Interobserver ICC was 0.993. Area under the curve (AUC) for differentiating cervical cancer from normal cervical stroma was 0.927. The feasible threshold value for AUC was determined as 2.221 with sensitivity of 84.62% and specificity of 83.66%. DATA CONCLUSION: 3D TSE APTw MRI is feasible in cervical cancer. Cervical cancer showed significantly higher APT values than normal cervix. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1318-1325.

[Monoenergetic Reconstructions Using Detector-based Spectral CT for Imaging of Small Lesions in the Rabbit VX2 Liver Cancer Models].

Objective To evaluate the value of virtual monoenergetic(monoE)using dual-layer detector spectrum CT in detecting small lesions in rabbit VX2 liver cancer models.Methods Hepatic VX2 double tumor models were established in 24 New Zealand white rabbits by CT-guided puncture. All the rabbits underwent CT scans by using dual-layer detector CT to generate conventional 120-keV polychromatic images and monoE images with energy levels ranging from 40 to 100 keV during the arterial phase. The quantity of the lesion and measurement of the lesion length as well as the objective evaluations[signal noise ratio(SNR)and contrast noise ratio(CNR)] and the subjective evaluations(overall image quality score)of the image quality were independently measured by two radiologists. The results were compared with pathological findings.Results Pathology confirmed that 30 lesions were successfully established,with an average size of(3.99±0.91)mm. Eighteen(47.40%)and 30(100%)lesions were detected by conventional images and monoE images with energy levels from 40 to 65 keV,respectively. The correlation between the length diameter of fresh pathological specimens and the measurements of lesion length diameter on 40(r=0.948,P=0.000),45(r=0.958,P=0.000),50(r=0.972,P=0.000),55(r=0.952,P=0.000),60(r=0.921,P=0.000),65 keV(r=0.917,P=0.000)monoE images was better than that on conventional images(r=0.206,P=0.270). The subjective evaluation scores of the quality of the 40,45,50,and 55 keV monoE images were 4.50(4.00,4.50)(P=0.000),5.00(5.00,5.00)(P=0.000),5.00(4.50,5.00)(P=0.000),and 4.00(4.00,4.50)(P=0.002),respectively,which were significantly higher than the conventional mixed energy images[3.00(2.50,3.00)]. The objective evaluation of image quality showed that the SNR and CNR of monoE images decreased with the increase of the energy level of the monoE image. The CNR of monoE images with 40(P=0.000),45(P=0.002),and 50 keV(P=0.011)were higher than that of the conventional image. The CNR of monoE images with 40(P=0.000),45(P=0.000),50(P=0.000),and 55 keV(P=0.002)were higher than that of the conventional images.Conclusion Dual-layer detector spectrum CT monoE image in the low-energy state of 45-50 keV can improve the detection rate of small lesions in rabbit hepatic VX2 tumor models with better noise control and provide better image quality compared with conventional polychromatic images.

Network Meta-Analysis on the Effects of DNA Damage Response-Related Gene Mutations on Overall Survival of Breast Cancer Based on TCGA Database.

The study was conducted for comparing the effects of 12 DNA damage response gene mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1, and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We searched the Cancer Genome Atlas (TCGA) database from inception to September 2016. Studies that investigated the association between 12 DNA damage responses related genes and BC consolidated into this Network meta-analysis, by comparing directly or indirectly to evaluate the hazard rate (HR) value and the surface under the cumulative sequence ranking curves (SUCRA). In total four articles were involved. Our results demonstrated 12 DNA damage response gene mutations were associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6-26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0; BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR = 11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI = 2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0; PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA results revealed that the mutation of MDC1 gene was related to the worst prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene mutations were associated to the poor prognosis in patients with BC and the BC patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118: 4728-4734, 2017. © 2017 Wiley Periodicals, Inc.

A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway.

OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III. CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM. CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy. KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.

[Performance of computer-assisted imaging system in detection of squamous intraepithelial lesion of uterine cervix].

OBJECTIVE: To evaluate the performance of computer-assisted imaging system in the detection of cervical squamous intraepithelial lesion and quality-assurance. METHODS: Manual PAP screening (n = 140 580) and image-assisted screening (n = 32 885) were compared for the detection rates of squamous cell abnormalities, the atypical squamous cells (ASC) to squamous intraepithelial lesion (SIL) ratio, the positive rates of high risk human papillomavirus (HR-HPV) test in the case of atypical squamous cells of undetermined significance (ASC-US), and the correlation between cytopathology and histopathology. RESULTS: Compared with manual screening, computer-assisted imaging system showed increased overall positive detection by 0.32%, decreased detection of ASC by 0.21%, increased detection of low-grade squamous intraepithelial lesion (LSIL) by 0.22%, increased detection of high-grade squamous intraepithelial lesion or worse (HSIL) by 0.31%, and decreased ASC to SIL ratio from 2.59 to 1.60. Computer-assisted imaging system did not change the HR-HPV positive rate of the patients who were ASC-US, or the coincidence rate between cytopathology and histopathology. Moreover, the productivity of the laboratory operation increased 58.33%. CONCLUSION: Computer-assisted imaging system significantly increases the overall positive detection rate of cervical SIL, improves accuracy and work efficiency of screening, decreases the ASC/SIL rate, and strengths the quality-assurance of laboratory testing.

[Expression and significance of p-AKT, p-GSK3ß and ß-catenin in epithelial carcinoma of ovary].

OBJECTIVE: To investigate the expressions of phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3ß (p-GSK3ß) and ß-catenin proteins and to evaluate their relationship with the clinical pathological characteristics in epithelial tumors of the ovary. METHODS: The expression of p-AKT, p-GSK3ß, and ß-catenin was detected with immunohistochemical staining (EnVision method) in 10 cases of benign epithelial neoplasia, 10 cases of borderline epithelial neoplasia and 70 cases of ovarian carcinoma. The relationship of the expression of p-AKT, p-GSK3ß and ß-catenin with the clinical pathological features was analyzed. RESULTS: The positive expression rates of p-AKT, p-GSK3ß and ß-catenin in epithelial ovarian carcinoma were 67.1% (47/70), 60.0% (42/70) and 71.4% (50/70), respectively. Compared to the results of benign and borderline epithelial neoplasia, the expression of the three proteins in carcinoma of the ovary was significantly different (all P < 0.05).Positive correlation was found between p-AKT and p-GSK3ß, p-GSK3ß and ß-catenin, and p-AKT and ß-catenin in epithelial ovarian carcinoma (r = 0.546, 0.581, 0.500, respectively; all P < 0.05). Compared to the results of benign and borderline epithelial neoplasia, the expression of p-AKT protein in epithelial ovarian carcinoma was significantly different (all P < 0.05). The expression of p-AKT was correlated with the differentiation of epithelial ovarian carcinoma (P < 0.05), but no relationship was found between its expression and histological classification and FIGO staging (P > 0.05). The expression of p-GSK3ß and ß-catenin in epithelial ovarian carcinoma were both higher than that in benign and borderline epithelial neoplasia (P < 0.05), and correlated with tumor differentiation and FIGO staging (P < 0.05), but no relationship were found between their expression with histological classification (P > 0.05). CONCLUSIONS: Positive correlations are found between p-AKT, p-GSK3ß and ß-catenin in epithelial ovarian carcinoma. The activation of ß-catenin is possibly correlated with inactivation of p-GSK3ß that binds to p-AKT.

MRI-based radiomics analysis improves preoperative diagnostic performance for the depth of stromal invasion in patients with early stage cervical cancer.

BACKGROUND: The depth of cervical stromal invasion is one of the important prognostic factors affecting decision-making for early stage cervical cancer (CC). This study aimed to develop and validate a T2-weighted imaging (T2WI)-based radiomics model and explore independent risk factors (factors with statistical significance in both univariate and multivariate analyses) of middle or deep stromal invasion in early stage CC. METHODS: Between March 2017 and March 2021, a total of 234 International Federation of Gynecology and Obstetrics IB1-IIA1 CC patients were enrolled and randomly divided into a training cohort (n = 188) and a validation cohort (n = 46). The radiomics features of each patient were extracted from preoperative sagittal T2WI, and key features were selected. After independent risk factors were identified, a combined model and nomogram incorporating radiomics signature and independent risk factors were developed. Diagnostic accuracy of radiologists was also evaluated. RESULTS: The maximal tumor diameter (MTD) on magnetic resonance imaging was identified as an independent risk factor. In the validation cohort, the radiomics model, MTD, and combined model showed areas under the curve of 0.879, 0.844, and 0.886. The radiomics model and combined model showed the same sensitivity and specificity of 87.9% and 84.6%, which were better than radiologists (sensitivity, senior = 75.7%, junior = 63.6%; specificity, senior = 69.2%, junior = 53.8%) and MTD (sensitivity = 69.7%, specificity = 76.9%). CONCLUSION: MRI-based radiomics analysis outperformed radiologists for the preoperative diagnosis of middle or deep stromal invasion in early stage CC, and the probability can be individually evaluated by a nomogram.

Three-dimensional turbo-spin-echo amide proton transfer-weighted and intravoxel incoherent motion MR imaging for type I endometrial carcinoma: Correlation with Ki-67 proliferation status.

BACKGROUND: To evaluate 3-dimensional amide proton transfer weighted (APTw) imaging for type I endometrial carcinoma (EC), and investigate correlations of Ki-67 labelling index with APTw and intravoxel incoherent motion (IVIM) imaging. METHODS: 54 consecutive patients suspected of endometrial lesions underwent pelvic APTw and IVIM imaging on a 3 T MR scanner. APTw values and IVIM-derived parameters (Dt, D*, f) were independently measured by two radiologists on 22 postoperative pathological confirmed of type I EC lesions. Results were compared between histological grades and Ki-67 proliferation groups. ROC analysis was performed. Pearson's correlation analysis was performed for APTw values and IVIM-derived parameters with Ki-67 labeling index. RESULTS: APTw values and Dt, D*, f of all type I EC were 2.9 ± 0.1%, 0.677 ± 0.027 × 10-3 mm2/s, 31.801 ± 11.492 × 10-3 mm2/s, 0.179 ± 0.050 with inter-observer ICC 0.996, 0.850, 0.956, 0.995, respectively. APTw values of Ki-67 low-proliferation group (<30%, n = 8) were 2.5 ± 0.2%, significantly lower than the high-proliferation group (>30%, n = 14) with APTw values of 3.1 ± 0.1% (p = 0.016). Area under the curve was 0.768. APTw values of type I EC were moderately positively correlated with Ki-67 labelling index (r = 0.583, p = 0.004). There was no significant difference of Dt (p = 0.843), D* (p = 0.262), f (p = 0.553) between the two groups. No correlation was found between IVIM-derived parameters and Ki-67 labelling index (Dt, p = 0.717; D* p = 0.151; f, p = 0.153). CONCLUSION: 3D TSE APTw imaging is a feasible approach for detecting type I EC. Ki-67 labeling index positively moderately correlates with APTw not with IVIM.

Non-invasive Differentiation of Endometrial Adenocarcinoma from Benign Lesions in the Uterus by Utilization of Amide Proton Transfer-Weighted MRI.

PURPOSE: To evaluate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging for differentiation of endometrial adenocarcinoma and uterine benign lesions. PROCEDURES: This prospective study enrolled 22 normal volunteers and 113 patients with suspicious uterine lesions, including endometrial adenocarcinoma, leiomyoma, and adenomyosis. Pelvic APTw MRI was performed on a 3-T MRI scanner with default APTw parameters. Two radiologists blindly evaluated uterine lesion APTw image quality by a 3-point Likert scale and independently measured APTw values on images with excellent to good image quality. Inter-reader agreement was evaluated. The Mann-Whitney U test with Bonferroni correction was used to compare the differences among different types of uterine lesions. A receiver operating characteristic analysis was performed. RESULTS: A total of 111 lesions (33 endometrial adenocarcinoma, 26 leiomyoma, and 52 adenomyosis lesions) from 99 patients revealing a majority of good quality with excellent inter-reader agreement were included for the image quality evaluation. APTw values of endometrial adenocarcinoma were 2.9 ± 0.1 %, significantly higher than those of leiomyoma (1.9 ± 0.1 %), adenomyosis (2.2 ± 0.1 %), and normal uterine myometrium (1.9 ± 0.1 %) (all p < 0.0001). The area under the receiver operating characteristic curve for differentiating endometrial adenocarcinoma from leiomyoma, adenomyosis, and myometrium was 0.87, 0.85, and 0.91, respectively. Feasible threshold APTw values of each group were determined as 2.4 %, 2.7 %, and 2.4 % with a sensitivity of 83.3 %, 76.7 %, and 83.3 % and a specificity of 83.3 %, 81.6 %, and 86.4 %, respectively. CONCLUSIONS: Malignant endometrial adenocarcinoma had significantly higher APTw values than leiomyoma, adenomyosis, and normal uterine myometrium. Our study adds to the growing body of validation on 3D APTw imaging and uterine lesions.

Diffusion-weighted imaging of cervical cancer: Feasibility of ultra-high b-value at 3T.

PURPOSE: We sought to evaluate the image quality and compare the signal intensity (SI) and apparent diffusion coefficient (ADC) maps of ultra-high b-value (2000 s/mm2; B2) images against those of 800 s/mm2 b-value (B1) images of diffusion-weighted imaging (DWI) for cervical cancer. METHOD: This study was approved by the institutional review board. Sixty patients diagnosed with cervical cancer by pathology were prospectively included. Female pelvic magnetic resonance imaging was performed using a 3 T magnetic resonance scanner; B1 and B2 images were obtained for evaluation. Two radiologists blinded to the scan parameters evaluated the images for signal loss in the background, spatial distortion, image ghosting, confidence in the lesion delineation, and overall image quality using a 5-point scoring system. The scores were compared using a paired Wilcoxon test. SI was measured in the B1 and B2 images for the tumour and normal reference tissues. Additionally, the SI contrast ratios were calculated and compared using the Mann-Whitney U test, the ADC values of tumours and normal tissues were measured, and the maximum tumour diameters were measured from the B1 and B2 images and compared with those from the T2-weighted images, which was the reference standard. RESULTS: The signal loss in the background, confidence of the lesion delineation and overall image quality scores were higher for the B2 images than for the B1 images (all p < 0.001). The contrast ratios of the tumour-to-normal SI were also higher for the B2 images than for the B1 images (p < 0.01). The mean ADC values derived from the B2 images showed better correlations with the tumour differentiation grades than those from the B1 images. The tumour diameters measured from the B2 images experienced less bias than those from the B1 images. CONCLUSIONS: B2 images of DWI are technically feasible to acquire and provide more promising additional information for the delineation of cervical cancer tumours than B1 images of the female pelvis.

DNMT3a promotes proliferation by activating the STAT3 signaling pathway and depressing apoptosis in pancreatic cancer.

BACKGROUND: Although aberrant DNA methyltransferase 3a (DNMT3a) expression is important to the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC), the role of DNMT3a in PDAC prognosis is not clarified yet due to the limited studies and lacking of underlying molecular mechanism. METHODS: The expression of DNMT3a was examined by immunohistochemistry in PDAC tissues. Gene expression profiles assays were conducted to explore the impact of DNMT3a on biological processes and signal pathways. Cell cycle and apoptosis were measured by flow cytometry. Western blotting and real-time qPCR assays were used to explore the impact of DNMT3a on expression of protein and mRNA related to cell cycle, STAT3 signaling pathway and apoptosis. RESULTS: DNMT3a was overexpressed and closely associated with poor outcomes of PDAC. DNMT3a knockdown restrained PDAC cell proliferation, induced cell cycle arrest and promoted apoptosis in vitro. Affymetrix GeneChip Human Transcriptome Array identified that the cell cycle-related process was most significantly associated with DNMT3a. DNMT3a knockdown induced G1-S phase transition arrest by decreasing the expression of cyclin D1, which was mediated by the reduction of IL8 and the subsequent inactivation of STAT3 signaling pathway. Furthermore, exogenous apoptosis was also promoted after DNMT3a knockdown, probably via up-regulation of DNA transcription and expression in CASP8. CONCLUSION: These findings indicate that DNMT3a plays an important role in PDAC progression. DNMT3a may serve as a prognostic biomarker and a therapeutic strategy candidate in PDAC.

Expression of soluble and functional snake venom fibrinolytic enzyme fibrolase via the co-expression of DsbC in Escherichia coli.

Fibrolase is a non-hemorrhagic zinc metalloproteinase found in southern copperhead snake venom (Agkistrodon contortrix contortrix). It is capable of degrading fibrin clots that result from purified fibrinogen or blood plasma. The DNA of fibrolase was amplified by recursive PCR, and cloned into the pET25b(+) expression vector. The effect of co-expression of signalless versions of catalysts or molecular chaperones FkpA, Skp and DsbC in cytoplasm was examined. When co-expressed with DsbC, compared to the totally insoluble inclusion bodies of fibrolase expressed separately, more than 90 % of recombinant fibrolase was soluble, according to denaturing polyacrylamide gel electrophoresis analysis. We also determined that FkpA and Skp had no effects on the solubility of target protein when co-expressed with fibrolase in Escherichia coli. Fibrolase was successfully purified using metal ion affinity chromatography and hydrophobic chromatography, and a maximum yield of 20 mg/L fibrolase was obtained. Fibrinolytic activity of recombinant fibrolase was demonstrated using fibrin plate assays and fibrinogen hydrolysis.

Synergistic Effects of Gold Nanocages in Hyperthermia and Radiotherapy Treatment.

Gold nanocages (GNCs) are a promising material that not only converts near infrared (NIR) light to heat for the ablation of tumors but also acts as a radiosensitizer. The combination of hyperthermia and radiotherapy has a synergistic effect that can lead to significant tumor cell necrosis. In the current study, we synthesized GNCs that offered the combined effects of hyperthermia and radiotherapy. This combination strategy resulted in increased tumor cell apoptosis and significant tumor tissue necrosis. We propose that GNCs can be used for clinical treatment and to potentially overcome resistance to radiotherapy by clearly increasing the antitumor effect.