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A ketamine/xylazine (K/X) mixture is widely used before and during experiments in rodents. However, the impact of short-term use of K/X mixture and its influences on data interpretation have rarely been discussed. In this study, we administered one shot of a K/X mixture and examined acute hepatic responses using biochemical analysis, histopathological examination, and non-invasive imaging to determine the delay required prior to further assessment of the liver to avoid confounding effects triggered by anaesthesia. After the K/X injection, aspartate aminotransferase (AST) in serum was significantly elevated from 3 to 48 h. Obstructed sinusoidal circulation lasting for 24 or 36 h was revealed by DCE-MRI and drug distribution analysis, respectively. Metabolic alterations were detected at 3 h by NMR analysis and FDG-PET. Moreover, ultrasonography showed that lipid droplet accumulation increased from 1 to 16 h and declined thereafter. Taken together, our findings show that the K/X mixture induces acute hepatotoxicity and metabolic disturbance, and these disturbances cause hemodynamical disorders in the liver. The required time interval for recovery from K/X impact was dependent on the chosen assay. It took at least 16 h for metabolic recovery and 36 h for recovery of sinusoidal circulation. However, the liver was not fully recovered from the injury within 48 h.

Purpose: Our purpose was to assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) and pelvic/abdominal magnetic resonance imaging (MRI) after concurrent chemoradiotherapy (CCRT) for posttherapy evaluation in patients with advanced cervical cancer., Methods: Patients with cervical squamous cell carcinoma, either with advanced FIGO stage or with positive pelvic or para-aortic lymph node (PALN), received PET/CT using [ 18 F]fluorodeoxyglucose and MRI including diffusion-weighted imaging between 2 and 3 months after CCRT completion. PET/CT were interpreted independently by two nuclear medicine physicians and MRI by two radiologists using the same scoring system. Active residual tumor was proven by pathological confirmation or disease progression on imaging studies within one year after CCRT and the disease regions were classified as local, regional, PALN, or distant. Patient-based and region-based comparison was performed using the receiver operating characteristic curve analysis., Results: The study included 55 patients and 15 (27%) patients had active residual tumor. The diagnostic performance of PET/CT is significantly superior to that of MRI in patient-based analysis (P = 0.025) and in the detection of local (P = 0.045) and regional (P = 0.014) disease. The patient-based sensitivity, specificity, and accuracy of PET/CT are 60%, 100%, and 89% while those of MRI are 27%, 100%, and 80%., Conclusions: PET/CT is superior to MRI for posttherapy evaluation in patients with advanced cervical cancer 2-3 months after definitive CCRT, mainly for the detection of residual local and regional disease. Patients with negative or equivocal results should be followed up regularly due to suboptimal sensitivities of imaging.

Purpose: The microvasculature of a tumor plays an important role in its response to radiation therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and blood oxygen level-dependent (BOLD) MRI are both sensitive to vascular characteristics. The present study proposed a partial irradiation approach to a xenograft tumor to investigate the intratumoral response to radiation therapy using DCE and BOLD MRI., Methods and Materials: TRAMP-C1 tumors were grown in C57BL/6J mice. Partial irradiation was performed on the distal half of the tumor with a single dose of 15 Gy. DCE MRI was performed to derive the endothelium transfer constant, K(trans), using pharmacokinetic analysis. BOLD MRI was performed using quantitative R2 measurements with carbogen breathing. The histology of the tumor was analyzed using hematoxylin and eosin staining and CD31 staining to detect endothelial cells. The differences between the irradiated and nonirradiated regions of the tumor were assessed using K(trans) values, ΔR2 values in response to carbogen and microvascular density (MVD) measurements., Results: A significantly increased K(trans) and reduced BOLD response to carbogen were found in the irradiated region of the tumor compared with the nonirradiated region (P<.05). Histologic analysis showed a significant aggregation of giant cells and a reduced MVD in the irradiated region of the tumor. The radiation-induced difference in the BOLD response was associated with differences in MVD and K(trans)., Conclusions: We demonstrated that DCE MRI and carbogen-challenge BOLD MRI can detect differential responses within a tumor that may potentially serve as noninvasive imaging biomarkers to detect microvascular changes in response to radiation therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Uncertainty in arterial input function (AIF) estimation is one of the major errors in the quantification of dynamic contrast-enhanced MRI. A blind source separation algorithm was proposed to determine the AIF by selecting the voxel time course with maximum purity, which represents a minimal contamination from partial volume effects. Simulations were performed to assess the partial volume effect on the purity of AIF, the estimation accuracy of the AIF, and the influence of purity on the derived kinetic parameters. In vivo data were acquired from six patients with hypopharyngeal cancer and eight rats with brain tumor. Results showed that in simulation the AIF with the highest purity is closest to the true AIF. In patients, the manually selection had reduced purity, which could lead to underestimations of K(trans) and V(e) and an overestimation of V(p) when compared with those obtained by the proposed blind source separation algorithm. The derived kinetic parameters in the tumor were more susceptible to the changes in purity when compared with those in the muscle. The animal experiment demonstrated good reproducibility in blind source separation-AIF derived parameters. In conclusion, the blind source separation method is feasible and reproducible to identify the voxel with the tracer concentration time course closest to the true AIF., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: To determine whether magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) are able to distinguish between adenocarcinoma originating from the uterine cervix and endometrium., Methods: Institutional review board approval and informed consent were obtained. From May 2006 to June 2008, 29 women 25-73 years old (mean age, 50.3 years) with a cervical biopsy yielding adenocarcinoma were enrolled for 3-T MR study with the imaging pulse-sequence protocol of T2-weighted imaging (T2WI) and dynamic contrast-enhanced (DCE) MRI and diffusion-weighted MRI (DWI, b = 0, 1000 sec/mm2). The extent and shapes of the tumor and ADC values were evaluated by two radiologists retrospectively. Surgical histopathology served as the reference standard of the tumor origin from the cervix (n = 22) or endometrium (n = 7). The Mann-Whitney U test was used for statistical comparison and receiver operating characteristic (ROC) analysis was used to obtain optimal ADC cut off values., Results: A longitudinal shape occurred significantly more frequently in endometrial cancer, and an oval shape was more frequently found in cervical cancer (p = 0.011). Mean ADC values were significantly lower in endometrial cancer (76.6 × 10(-5) mm2/sec) than in cervical cancer (96.9 × 10(-5) mm2/sec). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 70 × 10(-5) mm2/sec to distinguish cervical cancer from endometrial cancer., Conclusion: MRI may distinguish between most uterine adenocarcinoma originating from the cervix and endometrium using distinctive characteristics found on T2WI and DCE. When tumors show an ambiguous morphology, the ADC value of the tumor may be helpful for further differentiation.

Purpose: To assess the diagnostic accuracy of fused T2-weighted and high-b-value diffusion-weighted (DW) magnetic resonance (MR) images at 3 T for evaluation of myometrial invasion in patients with endometrial cancer., Materials and Methods: Institutional review board approval and informed consent were obtained. From May 2006 to October 2007, 48 consecutive patients aged 25-80 years (mean age, 57 years) who had endometrial cancer were prospectively enrolled for preoperative evaluation by using a 3-T MR unit. Two radiologists interpreted the depth of myometrial invasion on T2-weighted images, dynamic contrast material-enhanced MR images, and fused T2-weighted and DW MR images (b = 1000 sec/mm(2)). Statistical methods included kappa statistics for reader agreement, Pearson analysis for pathologic correlation, accuracy assessment, and receiver operating characteristic analysis for diagnostic performance comparison. Surgical pathologic findings were the reference standard., Results: Reader agreement was excellent for fused T2-weighted and DW images (weighted kappa, 0.79), with a significant pathologic correlation regarding the depth of myometrial invasion (r = 0.94, P < .0001). For assessing any myometrial involvement, addition of fused T2-weighted and DW imaging to dynamic contrast-enhanced or dynamic contrast-enhanced and T2-weighted imaging was significantly better compared with dynamic contrast-enhanced imaging alone (P < .001) or dynamic contrast-enhanced and T2-weighted (P = .001) imaging; T2-weighted imaging combined with fused T2-weighted and DW imaging also was better than dynamic contrast-enhanced and T2-weighted imaging (P = .001). Tumor apparent diffusion coefficients were 0.60-1.32 x 10(-3) mm(2)/sec (median, 0.75 x 10(-3) mm(2)/sec), with no significant correlation with the depth of myometrial invasion (P = .31, r = -0.15)., Conclusion: Fused T2-weighted and high-b-value DW images at 3 T can provide accurate information for preoperative evaluation of myometrial invasion., (RSNA, 2009)

Background: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. Methods: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39–60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. Results: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. Conclusions: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. Trial registration: ClinicalTrials.gov NCT04951921, registered 7 July 2021. Relevance statement: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. Key points: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Assessment of tumor extent and lymphatic metastasis of uterine carcinosarcomas is important for treatment planning.Purpose/hypothesis: To evaluate the diagnostic accuracy of 3.0T diffusion-weighted (DW) MRI for patients with uterine carcinosarcoma, in assessment of tumor extent and lymphatic metastasis.Study Type: Retrospective diagnostic accuracy study.Population: A consecutive cohort of 68 patients with pathologically proved carcinosarcoma between January 2006 and July 2014.Field Strength/sequence: 3T DW MRI.Assessment: Maximal tumor and uterus size, presence of deep myometrial invasion, cervical invasion, adnexal invasion, lymphadenopathy, and the apparent diffusion coefficient (ADC) values of each tumor were used. Histopathology was the gold standard.Statistical Tests: Diagnostic accuracy. Logistic regression.Results: In all, 38 patients entered the final analysis, with median age of 58 years (range, 35-79 years). The sensitivity and specificity in detecting deep myometrial invasion, cervical stromal invasion, adnexal invasion, as well as pelvic and para-aortic lymph node metastases were 65% and 72%, 91% and 85%, 50% and 100%, 33% and 89%, and 33% and 100%, respectively. The largest tumor diameters predicted deep myometrium invasion (anteroposterior direction, P = 0.004) and cervical stroma invasion (craniocaudal direction, P = 0.008). Tumor ADCmin significantly predicted the lymphovascular permeation (P = 0.025; odds ratio = 0.96).Data Conclusion: Preoperative DW MRI is useful to assess deep myometrial or cervical stromal invasion in uterine carcinosarcoma, yet the diagnostic performance for detecting adnexal invasion and lymphatic metastasis requires further improvement.Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a prognostic model of integrating whole-tumour apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging with human papillomavirus (HPV) genotyping in predicting the overall survival (OS) and disease-free survival (DFS) for women with stage IB-IV cervical cancer following concurrent chemoradiotherapy (CCRT).Methods: We retrospectively analysed three prospectively collected cohorts comprising 300 patients with stage IB-IV cervical cancer treated with CCRT in 2007-2014 and filtered 134 female patients who underwent MR imaging at 3.0 T for final analysis (age, 24-92 years; median, 54 years). Univariate and multivariate Cox regression analyses were used to evaluate the whole-tumour ADC histogram parameters, HPV genotyping and relevant clinical variables in predicting OS and DFS. The dataset was randomly split into training (n = 88) and testing (n = 46) datasets for construction and independent bootstrap validation of the models.Results: The median follow-up time for surviving patients was 69 months (range, 9-126 months). Non-squamous cell type, ADC10 <0.77 × 10-3 mm2/s, T3-4, M1 stage and high-risk HPV status were selected to generate a model, in which the OS and DFS for the low, intermediate and high-risk groups were significantly stratified (p < 0.0001). The prognostic model improved the prediction significantly compared with the International Federation of Gynaecology and Obstetrics (FIGO) stage for both the training and independent testing datasets (p < 0.0001).Conclusions: The prognostic model based on integrated clinical and imaging data could be a useful clinical biomarker to predict OS and DFS in patients with stage IB-IV cervical cancer treated with CCRT.Key Points: • ADC 10 is the best prognostic factor among ADC parameters in cervical cancer treated with CCRT • A novel prognostic model was built based on histology, ADC 10 , T and M stage and HPV status • The prognostic model outperforms FIGO stage in the survival prediction. [ABSTRACT FROM AUTHOR]

Background: To prospectively evaluate the value of positron emission tomography (PET) or integrated computed tomography (CT) and PET (PET/CT) in the management of documented or suspected recurrent ovarian cancer.Methods: Patients with ovarian cancer who had completed primary cytoreductive surgery and standard adjuvant chemotherapy were studied to evaluate the following indications: (1) CA125 elevation after complete remission with negative CT or magnetic resonance imaging (MRI) result; (2) post-therapy surveillance CT/MRI-detected suspicious lesions that guided biopsy was not feasible; (3) documented relapse for restaging prior to or after curative salvage therapy. The clinical impact of PET, as compared with those of CT/MRI, was determined on a per scan basis.Results: From 2002 to 2009, 73 patients were recruited, and 92 PET scans were performed. Up to June 2015, 53 patients had died of disease, four were alive with disease, and the remaining 16 were alive without disease. Among the 92 scans, PET had positive impacts in 72.8%, no clinical impacts in 21.7%, and negative impacts in 5.4%. For indication 1, the sensitivity and positive predictive value of PET in detecting recurrence were 80.0% and 92.3%, respectively. For indication 2, the sensitivity, specificity, positive predictive value, and negative predictive value of PET were 91.2%, 62.5%, 91.2%, and 62.5%, respectively. For indication 3, PET provided positive impact in 85.3% and negative impact in 2.9% of the 34 scans.Conclusion: PET has value in the management of suspected or documented recurrent ovarian cancer, with positive impacts on confirming recurrent status and offering a better treatment plan. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the efficacy of linear accelerator (LINAC)-based radiosurgery in the treatment of acoustic neuromas. In this retrospective study, we enrolled 75 patients with non-neurofibromatosis type 2 acoustic neuromas who were followed-up for more than 5years. The 75 patients were divided into 3 groups: patients with a newly diagnosed tumor; those with a residual tumor; and those with a recurrent tumor. The average follow-up period was 97.8months. The overall tumor progression-free rate was 92%, and corresponding rates among those with newly diagnosed tumors was 100%, residual tumors was 84.4%, and recurrent tumors was 92.8% (p =0.028). Lesion localization using CT scans correlated with a higher tendency for tumor progression than lesion localization using CT–MRI fusion images (15.6% versus 2.4%, respectively). Residual tumors treated with radiosurgery have a higher progression rate, and careful lesion localization using CT–MRI image fusion is required. [Copyright &y& Elsevier]

Abstract: Objective: Clinical outcomes of cervical cancer patients with distant lymph node (LN) metastases are poor. [18F] fluorodeoxyglucose positron emission tomography (PET) or PET/computed tomography (CT) scans could potentially benefit treatment plan. Methods: Patients with cervical cancer whose CT/magnetic resonance imaging (MRI)-based imaging showed limited metastases to para-aortic lymph node (PALN), inguinal (ILN), and/or supraclavicular (SLN) were prospectively enrolled to evaluate whether PET or PET/CT influenced management. The clinical impact of PET or PET/CT was determined on a patient basis. Results: Between November 2001 and April 2007, 47 patients were enrolled for suspected metastasis to PALN with (n =8) or without other distant nodal involvement (n =31), ILN (n =6), or SLN metastasis (n =2). Additional PET or PET/CT had positive clinical impact in 21 (44.7%) of the 47 study patients, 23 had no impact, and three had negative impact. Positive impact included disclosing additional curable sites (n =8), down-staging (n =6), offering metabolic biopsy (n =4) or change to palliation (n =3). The 2-year overall survival (OS) of the study patients was 56.9% with median follow-up time of 47.0 months (range: 8–71 months) in surviving patients. The 2-year OS rates for PALN (based on histology or CT/MRI-PET consensus) and histology-proven SLN metastasis were 50.6% and 24.7%, respectively. Two (40.0%) of the five patients with histology-proven ILN metastases had no evidence of disease. Conclusions: PET or PET/CT added benefit to primary treatment planning in cervical cancer with MRI-defined suspected distant nodal metastasis. [Copyright &y& Elsevier]