Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model.

BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

Pediatric diffuse intrinsic pontine glioma radiotherapy response prediction: MRI morphology and T2 intensity-based quantitative analyses.

OBJECTIVES: An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG. METHODS: We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis. RESULTS: Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SRdif), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively. CONCLUSION: Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response. CLINICAL RELEVANCE STATEMENT: Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG. KEY POINTS: Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population.

The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

Atypical primary central nervous system lymphoma and glioblastoma: multiparametric differentiation based on non-enhancing volume, apparent diffusion coefficient, and arterial spin labeling.

OBJECTIVES: To evaluate the multiparametric diagnostic performance with non-enhancing tumor volume, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) to differentiate between atypical primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). METHODS: One hundred and fifty-eight patients with pathologically confirmed typical PCNSL (n = 59), atypical PCNSL (hemorrhage, necrosis, or heterogeneous contrast enhancement, n = 29), and GBM (n = 70) were selected. Relative minimum ADC (rADCmin), mean (rADCmean), maximum (rADCmax), and rADCmax-min (rADCdif) were obtained by standardization of the contralateral white matter. Maximum cerebral blood flow (CBFmax) was obtained according to the ASL-CBF map. The regions of interests (ROIs) were manually delineated on the inner side of the tumor to further generate a 3D-ROI and obtain the non-enhancing tumor (nET) volume. The area under the curve (AUC) was used to evaluate the diagnostic performance. RESULTS: Atypical PCNSLs showed significantly lower rADCmax, rADCmean, and rADCdif than that of GBMs. GBMs showed significantly higher CBFmax and nET volume ratios than that of atypical PCNSLs. Combined three-variable models with rADCmean, CBFmax, and nET volume ratio were superior to one- and two-variable models. The AUC of the three-variable model was 0.96, and the sensitivity and specificity were 90% and 96.55%, respectively. CONCLUSION: The combined evaluation of rADCmean, CBFmax, and nET volume allowed for reliable differentiation between atypical PCNSL and GBM. KEY POINTS: • Atypical PCNSL is easily misdiagnosed as glioblastoma, which leads to unnecessary surgical resection. • The nET volume, ADC, and ASL-derived parameter (CBF) were lower for atypical PCNSL than that for glioblastoma. • The combination of multiple parameters performed well (AUC = 0.96) in the discrimination between atypical PCNSL and glioblastoma.

Metal-Cyclic Dinucleotide Nanomodulator-Stimulated STING Signaling for Strengthened Radioimmunotherapy of Large Tumor.

Combined treatment of immunotherapy and radiotherapy shows promising therapeutic effects for the regression of a variety of cancers. However, even multi-modality therapies often fail to antagonize the regression of large tumors due to the extremely immunosuppressive tumor microenvironment (TME). Here, a radioimmunotherapeutic paradigm based on stimulator of interferon genes (STING)-dependent signaling is applied to preclude large tumor progression by utilizing the metal-cyclic dinucleotide (CDN) nanoplatform, which integrates STING agonist c-di-AMP and immunomodulating microelement manganese (II) within the tannic acid nanostructure (TMA-NPs). As observed by magnetic resonance imaging, the localized administration of TMA-NPs effectively relieves hypoxia within TME and causes radical oxygen species overproduction and apoptosis in cancer cells after exposure to X-ray irradiation. The DNA fragments released from the apoptotic cells after the combined treatment augment the production of endogenous CDNs in cancer cells, hence significantly activating the STING-mediated pathway for stronger anti-tumor immunity. The localized therapy of TMA-NPs + X-ray not only inhibits the primary large tumor progression but also retards distant tumor growth by promoting dendritic cell maturation and activating cytotoxic immune cells whil suppressing immunosuppressive cells. Therefore, this work represents the combinatorial potency of TMA-NPs and X-rays on large tumor regression through strengthened STING-mediated radioimmunotherapeutics.

Facile synthesis of near-infrared responsive on-demand oxygen releasing nanoplatform for precise MRI-guided theranostics of hypoxia-induced tumor chemoresistance and metastasis in triple negative breast cancer.

BACKGROUND: Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion. METHODS: A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation. RESULTS: The near-infrared responsive on-demand oxygen releasing nanoplatform O2-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O2-PPSiI. CONCLUSIONS: Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC.

Comparison and risk factors analysis of multiple breast cancer screening methods in the evaluation of breast non-mass-like lesions.

OBJECTIVE: To compare multiple breast cancer screening methods for evaluating breast non-mass-like lesions (NMLs), and investigate new best screening method for breast non-mass-like lesions and the value of the lexicon of ACR BI-RADS in NML evaluation. METHODS: This retrospective study examined 253 patients aged 24-68 years who were diagnosed with breast NMLs and described the lexicon of ACR BI-RADS from April 2017 to December 2019. All lesions were evaluated by HHUS, MG, and ABUS to determine BI-RADS category, and underwent pathological examination within six months or at least 2 years of follow-up. The sensitivity, specificity, accuracy, positive predictive values (PPV), and negative predictive values (NPV) of MG, HHUS and ABUS in the prediction of malignancy were compared. Independent risk factors for malignancy were assessed using non-conditional logistic regression. RESULTS: HHUS, MG and ABUS findings significantly differed between benign and malignant breast NML, including internal echo, hyperechoic spot, peripheral blood flow, internal blood flow, catheter change, peripheral change, coronal features of ABUS, and structural distortion, asymmetry, and calcification in MG. ABUS is superior to MG and HHUS in sensitivity, specificity, PPV, NPV, as well as in evaluating the necessity of biopsy and accuracy in identifying malignancy. MG was superior to HHUS in specificity, PPV, and accuracy in evaluating the need for biopsy. CONCLUSIONS: ABUS was superior to HHUS and MG in evaluating the need for biopsy in breast NMLs. Compared to each other, HHUS and MG had their own relative advantages. Internal blood flow, calcification, and coronal plane feature was independent risk factors in NMLs Management, and different screening methods had their own advantages in NML management. The lexicon of ACR BI-RADS could be used not only in the evaluation of mass lesions, but also in the evaluation of NML.

Re-evaluation of high-risk breast mammography lesions by target ultrasound and ABUS of breast non-mass-like lesions.

OBJECTIVE: The purpose of this study was to reevaluate the high-risk breast non-mass-like lesions (NMLs) in mammography (MG) by target ultrasound (US) and Automated breast ultrasonography (ABUS), and to analyze the correlation between different imaging findings and the factors influencing the classification of lesions. METHODS: A total of 161 patients with 166 breast lesions were recruited in this retrospectively study. All cases were diagnosed as BI-RADS 4 or 5 by MG and as NML on ultrasound. While all NMLs underwent mammography, target US and ABUS before breast surgery or biopsy in the consistent position of breast. The imaging and pathological features of all cases were collected. All lesions were classified according to the lexion of ACR BI-RADS®. RESULTS: There were significant differences between benign and malignant breast NML in all the features of target US and ABUS. US, especially ABUS, was superior to MG in determining the malignant breast NML. There was a significant difference in the detection rate of calcification between MG and Target US (P < 0.001), and there was a significant difference in the detection rate of structural distortion between ABUS and MG (P < 0.001). CONCLUSIONS: Target US, especially ABUS, can significantly improve the sensitivity, specificity and accuracy of the diagnosis of high-risk NMLs in MG. The features of Target US and ABUS such as blood supply, hyperechogenicity, ductal changes, peripheral changes and coronal features could be employed to predict benign and malignant lesions. The coronal features of ABUS were more sensitive than those of Target HHUS in showing structural abnormalities. Target US was less effective than MG in local micro-calcification.

Performance of Dual-Source CT in Calculi Component Analysis: A Systematic Review and Meta-Analysis of 2151 Calculi.

OBJECTIVE: To evaluate the performance of dual-source computed tomography (DSCT) in the component analysis of all types of calculi by doing a systematic review and meta-analysis. METHODS: We searched MEDLINE, Embase, Scopus, and CNKI up to February 28, 2020, for in vivo studies investigating the performance of DSCT in the component analysis of calculi. We pooled the sensitivity, specificity, and areas under the summary receiver operating characteristic (AUROC) curves using a random-effect model in the meta-analysis. Publication bias was evaluated using Deek's funnel plot asymmetry test. RESULTS: This analysis included a total of 37 studies in 1840 patients with 2151 calculi (462 uric acid [UA], 1383 calcium oxalate [CaOx], 55 cystine [Cys], 197 hydroxyapatite [HA], and 54 struvite [SV]). Using DSCT, the pooled accuracy for diagnosing UA (sensitivity, 0.95; specificity, 0.99), CaOx (0.98; 0.93), Cys (0.99; 0.99), HA (0.91; 0.99), and SV (0.42; 0.98) was calculated, respectively. The AUROC value was 0.99, 0.99, 1.00, 0.99, and 0.93, respectively. The P values for publication bias test were .49, .70, .07, .04, and .19, respectively. CONCLUSION: Dual-source computed tomography has high sensitivity and specificity for the component analysis of UA, CaOx, Cys, and HA calculi in vivo. This tool may have the potential to replace the current analysis tool in vitro in diagnosing calculi.

Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2.

BACKGROUND: The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China. METHODS: All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People's Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18-86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1-6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution. FINDINGS: The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3-4 days. CONCLUSION: SARS-CoV-2 infection can be confirmed based on the patient's history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia.

Pelvic insufficiency fracture or bone metastasis after radiotherapy for cervical cancer? The added value of DWI for characterization.

OBJECTIVES: We sought to determine the added value of diffusion-weighted magnetic resonance imaging (DWI) in the differentiation of pelvic insufficiency fracture (PIF) from bone metastasis after radiotherapy in cervical cancer patients. METHODS: In the present study, 42 cervical cancer patients after radiotherapy with 61 bone lesions (n = 40, PIFs; n = 21, bone metastasis) were included. Conventional MRI and DWI were performed in all patients. For qualitative imaging diagnosis, two sets of images were reviewed independently by three observers, including a conventional MRI set (unenhanced T1-weighted, T2-weighted, and enhanced T1-weighted images) and a DWI set (conventional MRIs, DW images, and ADC maps). The mean ADC value of each lesson was measured on ADC maps. The diagnostic performance was assessed by using the area under the receiver operating characteristic curve (Az), and sensitivity and specificity were determined. RESULTS: For all observers, the Az value and sensitivity of the DWI set showed improvement compared with the conventional MRI set. The observer who had the least experience (3 years) demonstrated significant improvement in diagnostic performance with the addition of DWI; Az value increased from 0.804 to 0.915 (p = 0.042) and sensitivity increased from 75.0 to 92.5% (p = 0.035). The mean ADCs of the PIFs were significantly higher than the bone metastases (p < 0.001); ADC values > 0.97 × 10-3 mm2/s yielded an Az of 0.887, a sensitivity of 92.5%, and a specificity of 76.2%. CONCLUSIONS: The addition of DWI to conventional MRI improved the differentiation of PIF from bone metastasis after RT in patients with cervical cancer. KEY POINTS: • DWI showed additive value to conventional MRI in the differentiation of PIF from bone metastasis after RT. • For qualitative diagnosis, the addition of DWI can improve diagnostic performance compared with conventional MRI alone and can particularly improve the sensitivity. • Quantitative ADC assessment showed potential value for identifying PIF from bone metastasis.

Performing IVIM-DWI using the multifunctional nanosystem for the evaluation of the antitumor microcirculation changes.

OBJECTIVES: There is a controversy about the D* and f values of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for mid- and long-term efficacy monitoring of tumor blood perfusion. To monitor the antitumor efficacy of the F/A-PLGA@DOX/SPIO nanosystem via IVIM-DWI and to explore the value of parameters pseudo-diffusion (D*) and fraction of pseudo-diffusion (f) for evaluating therapeutic effect in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty-six A549 tumor-bearing mice were divided randomly into three groups (each n = 12). Group 1 (G1) was injected with saline (the control group). Group 2 (G2) and group 3(G3) were injected with DOX and F/A-PLGA@DOX/SPIO, respectively. Each group underwent IVIM-DWI scanning at baseline and 3, 14, 21, and 28 days after treatment. D* and f values were derived using GE AW 4.5 post-processing station. All mice were sacrificed for pathological examination. RESULTS: The D* value of all three groups showed an upward trend, with the highest increase in G1 and the lowest in G3. Conversely, the f value of all groups trended to decrease within 7 days, of which G3 showed the most significant decline. Immunohistochemical staining revealed that vascular endothelial growth factor (VEGF)-positive staining rate and the microvessel density (MVD) of the tumors in G3 were significantly lower than those of the other groups (P < 0.05). The D* and f values were significantly and positively correlated to CD31 (r = 0.654, P < 0.001; r = 0.712, P < 0.001) and VEGF (r = 0.694, P < 0.001; r = 0.664, P < 0.001). CONCLUSION: IVIM-DWI-derived parameters D* and f are valuable indicators for the evaluation of the antitumor microcirculation changes of multifunctional nanosystem.

Novel SPEG variant cause centronuclear myopathy in China.

BACKGROUND: Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Centronuclear myopathy is a kind of disease difficult to diagnose due to its genetic diversity. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported. METHODS: A radiograph test, ultrasonic test, and biochemical tests were applied to clinical diagnosis of CNM. We performed trio medical exome sequencing of the family and conservation analysis to identify variants. RESULTS: We report a pair of severe CNM twins with the same novel homozygous SPEG variant c. 8710A>G (p.Thr2904Ala) identified by clinical trio medical exome sequencing of the family and conservation analysis. The twins showed clinical symptoms of facial weakness, hypotonia, arthrogryposis, strephenopodia, patent ductus arteriosus, and pulmonary arterial hypertension. CONCLUSIONS: Our report expands the clinical and molecular repertoire of CNM and enriches the variant spectrum of the SPEG gene in the Chinese population and helps us further understand the pathogenesis of CNM.

Monitoring tumour microenvironment changes during anti-angiogenesis therapy using functional MRI.

OBJECTIVE: This study aims to explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in assessing vessel function and tumour aggressiveness during anti-angiogenesis treatment. MATERIALS AND METHODS: A colon cancer xenograft model was established in BALB/C nude mice with the HCT116 cell line. Sixteen mice were randomly divided into Group A and Group B, which were treated with saline or bevacizumab by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th days and underwent DCE-MRI and BOLD-MRI examinations before and on the 3rd, 6th, 9th, 12th and 15th days after treatment. Group C was treated with oxaliplatin monotherapy, and Group D was treated with bevacizumab and oxaliplatin as a point of comparison for therapeutic effects. The pathological examinations included HE, HIF-1α, fibronectin and TUNEL staining, as well as α-SMA and CD31 double staining. One-way analysis of variance and correlation analysis were the main methods used for statistical analysis. RESULTS: Group D manifested the highest tumour inhibition rate and smallest tumour volume on day 15, followed by Group C, Group B and Group A. Ktrans (F = 81.386, P < 0.001), Kep (F = 45.901, P < 0.001), Ve (F = 384.290, P < 0.001) and R2* values (F = 89.323, P < 0.001) showed meaningful trends with time in Group B but not Group A. The Ktrans values and tumour vessel maturity index (VMI) were higher than baseline values 3-12 days after bevacizumab treatment. The CD31 positive staining rate and VMI had the strongest correlations with Ktrans values, followed by AUC180, Ve and Kep values. The R2* value positively correlated with the positive staining rates of HIF-1α and fibronectin. CONCLUSION: Intermittent application of low-dose anti-angiogenic inhibitor treatment may help improve the effect of chemotherapy by reducing hypoxia-related treatment resistance and improving drug delivery. DCE-MRI is useful for evaluating vessel maturity and vascular normalization, while BOLD-MRI may help to predict tumour hypoxia and metastatic potential after anti-vascular treatment.

Intravoxel Incoherent Motion and Arterial Spin Labeling MRI Analysis of Reversible Unilateral Ureteral Obstruction in Rats.

BACKGROUND: Renal fibrosis is a common consequence of chronic kidney disease (CKD) and is the mechanism by which various forms of CKD progress to endstage renal failure. Accurate assessment of renal fibrosis is important for treatment. PURPOSE: To measure longitudinal changes of intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) before and after reversible unilateral ureteral obstruction in an animal model. STUDY TYPE: Self-controlled animal study. ANIMAL MODEL: Surgical obstruction of the ureters was performed and then removed after 5 days. Rats were scanned on Days 0, 1, 3, and 5 after creating the obstruction and on Days 4, 7, and 12 after releasing the obstruction. FIELD STRENGTH/SEQUENCE: 3.0T/IVIM/ASL. ASSESSMENT: The apparent diffusion coefficient (ADC), pure molecular diffusion (D), perfusion fraction (f), pseudodiffusion (D*), and renal blood flow (RBF) obtained from the ASL were measured. STATISTICAL TESTS: Using SPSS v. 20.0 software, P < 0.05 were considered statistically significant. The data from each timepoint were compared using one-way analysis of variance and correlation analysis was applied to various parameters. RESULTS: The postobstruction kidneys showed renal tubule swelling and increased collagen fiber content. Renal tubule swelling was relieved after reversing the obstruction, but Masson staining and cell density analysis revealed progressive changes that were primarily localized to the medulla. In general, ADC, D, f, D*, and RBF decreased with time during the 5 days of obstruction, and increased after release of the obstruction. ADC positively correlated with D, f, D*, and RBF (r = 0.415, r = 0.634, r = 0.465 r = 0.586, P < 0.001, respectively) in the cortex in this study. Also, ADC showed a positive correlation with D, f, and D* (r = 0.724, r = 0.749, r = 0.151, P < 0.001, respectively) in the medulla. DATA CONCLUSION: Kidney perfusion was the major factor affecting ADC. Functional imaging may be useful for following progression of CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:288-296.

Ginsenoside F1 promotes angiogenesis by activating the IGF-1/IGF1R pathway.

Ischemic stroke is one of the most lethal and highly disabling diseases that seriously affects the human health and quality of life. A therapeutic angiogenic strategy has been proposed to alleviate ischemia-induced injury by promoting angiogenesis and improving cerebrovascular function in the ischemic regions. The insulin-like growth factor 1 (IGF-1)/insulin-like growth factor 1 receptor (IGF1R) axis is crucial for cerebral angiogenesis and neurogenesis. However, effective drugs that prevent cerebral ischemic injury by inducing cerebral angiogenesis via activation of the IGF1R pathway are lacking. Here, we screened a pro-angiogenic agent ginsenoside F1 (GF1), a ginseng saponin isolated from a traditional Chinese medicine that was widely used in ischemic stroke treatment. It promoted the proliferation, mobility and tube formation of human umbilical vein endothelial cells and human brain microvascular endothelial cells, as well as pericytes recruitment to the endothelial tubes. GF1 stimulated vessel sprouting in the rat arterial ring and facilitated neovascularization in chicken embryo chorioallantoic membrane (CAM). In the in vivo experiments, GF1 rescued the axitinib-induced vascular defect in zebrafish. It also increased the microvessel density (MVD) and improved focal cerebral blood perfusion in the rat middle cerebral artery occlusion (MCAO) model. Mechanism studies revealed that GF1-induced angiogenesis depended on IGF1R activation mediated by the autocrine IGF-1 loop in endothelial cells. Based on our findings, GF1-induced activation of the IGF-1/IGF1R pathway to promote angiogenesis is an effective approach to alleviate cerebral ischemia, and GF1 is a potential agent that improves cerebrovascular function and promotes recovery from ischemic stroke.

Detection of Hyperacute Reactions of Desacetylvinblastine Monohydrazide in a Xenograft Model Using Intravoxel Incoherent Motion DWI and R2* Mapping.

OBJECTIVE: This study aimed to investigate the feasibility of intravoxel incoherent motion (IVIM) DWI and R2* (transverse relaxation rate) mapping to monitor the hyperacute therapeutic efficacy of desacetylvinblastine monohydrazide (DAVLBH) on an experimental hepatocellular carcinoma mouse model within 24 hours. MATERIALS AND METHODS: Forty-four mice were implanted with hepatocellular carcinoma and divided into three random groups. A treatment group and a control group underwent IVIM-DWI and R2* mapping examinations before and after a single injection of DAVLBH or saline at 1, 2, 4, and 24 hours. The pathology group was set for pathologic analysis, including H and E staining and CD31 and hypoxia-inducible factor (HIF)-1α immunohistochemical staining. RESULTS: DAVLBH caused hyperacute disruptions on the tumor capillaries in the treatment group. Water molecule diffusion (D), microcirculation perfusion (D*), and perfusion fraction (f) decreased initially but then gradually recovered to the baseline level by 24 hours after the first injection of DAVLBH. In contrast, R2* increased dramatically at 1 hour and then gradually decreased from 1 hour to 24 hours after treatment. D*, f, and D showed similar trends and were positively correlated with CD31 expression (r = 0.868, 0.721, and 0.730, respectively), but were negatively correlated with HIF-1α expression (r = -0.784, -0.737, and -0.673, respectively). R2* showed a negative correlation with CD31 expression (r = -0.823) and a positive correlation with HIF-1α expression (r = 0.791). CONCLUSION: Both IVIM-DWI and R2* mapping can adequately detect the vascular-disrupting effect of DAVLBH as early as 1 hour after injection in a mouse xenograft model. Moreover, D* and R2* are the two most sensitive hemodynamic parameters and can monitor the hyperacute changes associated with DAVLBH treatment in vivo.

Establishment of the Prognosis Predicting Signature for Endometrial Cancer Patient.

BACKGROUND Novel biomarkers provide clinicians more critical information on tumor genetic features and patients' prognosis. Here, we aimed to establish prognosis-predicting signatures for endometrial carcinoma (EC) patients based on the miRNA information. MATERIAL AND METHODS The Cancer Genome Atlas (TCGA) website was available for dataset extraction. Prognosis-associated miRNAs were generated by univariate Cox regression test. Online websites were used to predict the targeted genes of these enrolled miRNAs. The miRNA-mRNA network was described by Cytoscape software, while the relevant signaling pathways of these targeted genes were enriched by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS The miRNA-based overall survival (OS) and recurrence-free survival (RFS) predicting signatures were constructed by LASSO Cox regression analyses, respectively, by which, the endometrial carcinoma patients were separated into high- and low-risk groups in both the discovery and validation sets. Univariate Cox regression analyses suggested that these high-risk patients had elevated death and recurrence risk compared to low-risk patients. In addition, multivariate Cox regression analysis confirmed that our signatures were independent prognosticate factors with or without clinicopathological features for endometrial carcinoma patients. Moreover, the miRNA-mRNA network was displayed by Cytoscape software, and the pathway enrichment analyses found that the targeted genes of these enrolled miRNAs were enriched in tumor progression and drug resistance-related pathways. CONCLUSIONS The OS and RFS predicting classifiers serve as independent prognosis-associated determiners for EC patients.

Diagnostic Performance of Perfusion Computed Tomography for Differentiating Lung Cancer from Benign Lesions: A Meta-Analysis.

BACKGROUND Numerous studies have explored diagnosis of pulmonary nodules using perfusion computed tomography (CT); however, findings were not always consistent between studies. Th e present study aimed to summarize evidence on the diagnostic value of perfusion CT for distinguishing between lung cancer and benign lesions. MATERIAL AND METHODS We performed a systematic literature search on lung cancer and benign pulmonary lesions performed with perfusion CT. The searches were undertaken in English or Chinese language in Medline, PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure database from Jan 2010 to Nov 2018. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) of blood volume (BV), blood flow (BF), mean transit time (MTT), and permeability surface (PS) were calculated using Review Manager 5.3. Publication bias, sensitivity, specificity, and the area under the curve (AUC) were calculated using Stata12.0. RESULTS Fourteen studies comprising 1032 malignant and 447 benign pulmonary lesions were analyzed. Lung cancer had higher BV, BF, MTT, and PS values than benign lesions. SMDs and 95% CIs of BV, BF, MTT, and PS were 2.29 (1.43, 3.16), 0.50 (0.14, 0.86), 0.55 (0.39, 0.72), and 1.21 (0.87, 1.56), respectively. AUC values of BV and PS were 0.92 (0.90, 0.94) and 0.83 (0.80, 0.86), respectively. CONCLUSIONS CT perfusion imaging is a valuable technique for the diagnosis of pulmonary nodules. Lung cancer had higher perfusion and permeability than benign lesions. The evidence suggests blood volume is the best surrogate marker for characterizing the blood supply, while permeability surface has a high specificity in quantifying the vascular permeability.