Role of Additional MRI-Based Morphologic Measurements on the Performance of VI-RADS for Muscle-Invasive Bladder Cancer.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. PURPOSE: To investigate additional role of morphological (MOR) measurements to VI-RADS for the detection of muscle-invasive bladder cancer (MIBC) with mpMRI. STUDY TYPE: Retrospective. POPULATION: A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted imaging with fast-spin-echo sequence, spin-echo-planar diffusion-weighted imaging and dynamic contrast-enhanced imaging with fast 3D gradient-echo sequence. ASSESSMENT: VI-RADS score and MOR measurement including tumor location, number, stalk, cauliflower-like surface, type of tumor growth, tumor-muscle contact margin (TCM), tumor-longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3-year, 8-year, and 15-year experience of bladder MRI, respectively) who were blinded to histopathology. STATISTICAL TESTS: Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI-RADS. A P-value <0.05 was considered statistically significant. RESULTS: TCM (OR 9.98; 95% confidence interval [CI] 4.77-20.8), TCI (OR 5.72; 95% CI 2.37-13.8), and TLL (OR 3.35; 95% CI 1.40-8.03) were independently associated with MIBC at multivariable LR analysis. VI-RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI-RADS at DCA. Specially in VI-RADS-defined equivocal lesions, MOR-based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. DATA CONCLUSION: MOR measurements improved the performance of VI-RADS in detecting MIBC with mpMRI, especially for equivocal lesions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Ca2+ -independent transmission at the central synapse formed between dorsal root ganglion and dorsal horn neurons.

A central principle of synaptic transmission is that action potential-induced presynaptic neurotransmitter release occurs exclusively via Ca2+ -dependent secretion (CDS). The discovery and mechanistic investigations of Ca2+ -independent but voltage-dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here, we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons in vitro, (i) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS (up to 87%) and CDS; (ii) CiVDS-mediated EPSCs are independent of extracellular and intracellular Ca2+ ; (iii) CiVDS is faster than CDS in vesicle recycling with much less short-term depression; (iv) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity-induced EPSCs is mediated by CiVDS in a central synapse.

Biopsy-free AI-aided precision MRI assessment in prediction of prostate cancer biochemical recurrence.

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.

Regulating quantal size of neurotransmitter release through a GPCR voltage sensor.

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Gißγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y12(D76/D127) → Gißγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.

Enhanced anti-glioma efficacy of biodegradable periodic mesoporous organosilica nanoparticles through target delivery of chemotherapeutics.

Glioma is the most common malignant tumor of the brain and enhancing the efficacy of chemotherapy in glioma is critical for improving patients' prognosis. In this study, a glioma-targeting drug delivery system is constructed using biodegradable periodic mesoporous organosilica nanoparticles (PMO) that are modified with lactoferrin (Lf) ligands. The obtained PMO is doped with thioether groups and can be degraded in the high concentration of glutathione in tumor cells. The surface area and pore volume of PMO are 772 cm2/g and 0.98 cm3/g, respectively and the loading capacity of doxorubicin (Dox) is as high as 20%. The results of the confocal laser scanning microscope show that the uptake of PMO-Lf@Dox by C6 cells is higher than PMO@Dox. The quantitative analysis of the flow cytometer further demonstrates that more PMO-Lf@Dox enter C6 cells, indicating that the modification of lactoferrin can significantly increase the uptake of C6 cells. Finally, the therapeutic efficacy results show that Lf-modified PMO enhances the inhibitory effect of Dox on C6 cells when incubated for 24 h and 72 h. In summary, this lactoferrin receptor-mediated PMO drug carrier with biodegradability in glutathione in tumor cells can be used to enhance drug delivery into glioma without long-term accumulation in vivo. In this study, a glioma-targeting drug delivery system is constructed using periodic mesoporous organosilica nanoparticles (PMO) that modified with lactoferrin (Lf) ligands. This lactoferrin receptor-mediated PMO drug carrier can be used to enhance drug delivery into brain glioma.

Diagnosis, treatment and genetic analysis of an elderly patient with Gaucher's disease characterized by marked multiple bone destruction.

Gaucher's disease is a rare autosomal recessive genetic disease. Due to the decrease or lack of glucocerebrosidase (GBA) activity in lysosome caused by the mutation of GBA gene, its substrate glucocerebroside is detained in lysosome, resulting in clinical manifestations of liver, spleen, kidney, bone, hematopoietic system and even nervous system involvement. Here, we report a case of elderly patient presenting marked multiple bone destruction, with childhood medical history of splenectomy and "osteomyelitis". The patient has a significantly enlarged liver, accompanied by anemia, thrombocytopenia and osteopenia. Laboratory studies show this patient has low blood GBA activity and high glucosyl sphingosine level and increased chitotriosidase activity. Genetic testing revealed a homozygous missense variant NM_001005741.2 c.770A>G (p.Asp257Gly) in the patient's GBA gene. After 6 months of enzyme replacement therapy, the patient's platelets returned to normal, anemia improved, and liver volume decreased. Further detections show that the mother and brothers of the patient have heterozygous mutations at this locus, which is consistent with Mendelian inheritance law. Although this variant has not been reported in literatures or database, both clinical manifestations, characteristics of enzymology and biomarkers, and the effect of enzyme replacement therapy support the diagnosis of Gaucher's disease. The Asp257Gly variant is therefore assessed as a clinical pathogenic variant. This study expands the spectrum of the GBA gene variants. The diagnosis and treatment process of this case also provide reference for the early identification, diagnosis and early treatment of this kind of patients.

DCE-MRI based radiomics nomogram for preoperatively differentiating combined hepatocellular-cholangiocarcinoma from mass-forming intrahepatic cholangiocarcinoma.

OBJECTIVE: To establish a radiomics nomogram based on dynamic contrast-enhanced (DCE) MR images to preoperatively differentiate combined hepatocellular-cholangiocarcinoma (cHCC-CC) from mass-forming intrahepatic cholangiocarcinoma (IMCC). METHODS: A total of 151 training cohort patients (45 cHCC-CC and 106 IMCC) and 65 validation cohort patients (19 cHCC-CC and 46 IMCC) were enrolled. Findings of clinical characteristics and MR features were analyzed. Radiomics features were extracted from the DCE-MR images. A radiomics signature was built based on radiomics features by the least absolute shrinkage and selection operator algorithm. Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical model. The radiomics signature and significant clinicoradiological variables were then incorporated into the radiomics nomogram by multivariate logistic regression analysis. Performance of the radiomics nomogram, radiomics signature, and clinical model was assessed by receiver operating characteristic and area under the curve (AUC) was compared. RESULTS: Eleven radiomics features were selected to develop the radiomics signature. The radiomics nomogram integrating the alpha fetoprotein, background liver disease (cirrhosis or chronic hepatitis), and radiomics signature showed favorable calibration and discrimination performance with an AUC value of 0.945 in training cohort and 0.897 in validation cohort. The AUCs for the radiomics signature and clinical model were 0.848 and 0.856 in training cohort and 0.792 and 0.809 in validation cohort, respectively. The radiomics nomogram outperformed both the radiomics signature and clinical model alone (p < 0.05). CONCLUSION: The radiomics nomogram based on DCE-MRI may provide an effective and noninvasive tool to differentiate cHCC-CC from IMCC, which could help guide treatment strategies. KEY POINTS: • The radiomics signature based on dynamic contrast-enhanced magnetic resonance imaging is useful to preoperatively differentiate cHCC-CC from IMCC. • The radiomics nomogram showed the best performance in both training and validation cohorts for differentiating cHCC-CC from IMCC.

Ca2+-independent but voltage-dependent quantal catecholamine secretion (CiVDS) in the mammalian sympathetic nervous system.

Action potential-induced vesicular exocytosis is considered exclusively Ca2+ dependent in Katz's Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+-independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains elusive. Here, by combining multiple independent recordings, we report that [1] CiVDS robustly presents in the sympathetic nervous system, including sympathetic superior cervical ganglion neurons and slice adrenal chromaffin cells, [2] uses voltage sensors of Ca2+ channels (N-type and novel L-type), and [3] contributes to catecholamine release in both homeostatic and fight-or-flight like states; [4] CiVDS-mediated catecholamine release is faster than that of Ca2+-dependent secretion at the quantal level and [5] increases Ca2+ currents and contractility of cardiac myocytes. Together, CiVDS presents in the sympathetic nervous system with potential physiological functions, including cardiac muscle contractility.

Dynamin 1 Restrains Vesicular Release to a Subquantal Mode In Mammalian Adrenal Chromaffin Cells.

Dynamin 1 (dyn1) is required for clathrin-mediated endocytosis in most secretory (neuronal and neuroendocrine) cells. There are two modes of Ca2+-dependent catecholamine release from single dense-core vesicles: full-quantal (quantal) and subquantal in adrenal chromaffin cells, but their relative occurrences and impacts on total secretion remain unclear. To address this fundamental question in neurotransmission area using both sexes of animals, here we report the following: (1) dyn1-KO increased quantal size (QS, but not vesicle size/content) by ≥250% in dyn1-KO mice; (2) the KO-increased QS was rescued by dyn1 (but not its deficient mutant or dyn2); (3) the ratio of quantal versus subquantal events was increased by KO; (4) following a release event, more protein contents were retained in WT versus KO vesicles; and (5) the fusion pore size (dp) was increased from ≤9 to ≥9 nm by KO. Therefore, Ca2+-induced exocytosis is generally a subquantal release in sympathetic adrenal chromaffin cells, implying that neurotransmitter release is generally regulated by dynamin in neuronal cells.SIGNIFICANCE STATEMENT Ca2+-dependent neurotransmitter release from a single vesicle is the primary event in all neurotransmission, including synaptic/neuroendocrine forms. To determine whether Ca2+-dependent vesicular neurotransmitter release is "all-or-none" (quantal), we provide compelling evidence that most Ca2+-induced secretory events occur via the subquantal mode in native adrenal chromaffin cells. This subquantal release mode is promoted by dynamin 1, which is universally required for most secretory cells, including neurons and neuroendocrine cells. The present work with dyn1-KO mice further confirms that Ca2+-dependent transmitter release is mainly via subquantal mode, suggesting that subquantal release could be also important in other types of cells.

Radiomic Features at Contrast-enhanced CT Predict Recurrence in Early Stage Hepatocellular Carcinoma: A Multi-Institutional Study.

Background Early stage hepatocellular carcinoma (HCC) is the ideal candidate for resection in patients with preserved liver function; however, cancer will recur in half of these patients and no reliable prognostic tool has been established. Purpose To investigate the effectiveness of radiomic features in predicting tumor recurrence after resection of early stage HCC. Materials and Methods In total, 295 patients (median age, 58 years; interquartile range, 50-65 years; 221 men) who underwent contrast material-enhanced CT and curative resection for early stage HCC that met the Milan criteria between February 2009 and December 2016 were retrospectively recruited from three independent institutions. Follow-up consisted of serum α-fetoprotein level, liver function tests, and dynamic imaging examinations every 3 months during the first 2 years and then every 6 months thereafter. In the development cohort of 177 patients from institution 1, recurrence-related radiomic features were computationally extracted from the tumor and its periphery and a radiomics signature was built with least absolute shrinkage and selection operator regression. Two models, one integrating preoperative and one integrating pre- and postoperative variables, were created by using multivariable Cox regression analysis. An independent external cohort of 118 patients from institutions 2 and 3 was used to validate the proposed models. Results The preoperative model integrated radiomics signature with serum α-fetoprotein level and tumor number; the postoperative model incorporated microvascular invasion and satellite nodules into the above-mentioned predictors. In both study cohorts, two radiomics-based models provided better predictive performance (concordance index ≥0.77, P < .05 for all), lower prediction error (integrated Brier score ≤0.14), and larger net benefits, as determined by means of decision curve analysis, than rival models without radiomics and widely adopted staging systems. The radiomics-based models gave three risk strata with high, intermediate, or low risk of recurrence and distinct profiles of recurrent tumor number. Conclusion The proposed radiomics models with pre- and postresection features helped predict tumor recurrence for early stage hepatocellular carcinoma. © RSNA, 2020 Online supplemental material is available for this article.

Direct Comparison of Four Presurgical Stratifying Schemes for Prediction of Microvascular Invasion in Hepatocellular Carcinoma by Gadoxetic Acid-Enhanced MRI.

BACKGROUND: Microvascular invasion (MVI) is implicated in the poor prognosis of hepatocellular carcinoma (HCC). Presurgical stratifying schemes have been proposed for HCC-MVI but lack external validation. PURPOSE: To perform external validation and comparison of four presurgical stratifying schemes for the prediction of MVI using gadoxetic acid-based MRI in a cohort of HCC patients. STUDY TYPE: Retrospective. SUBJECTS: Included were 183 surgically resected HCCs from patients who underwent pretreatment MRI. FIELD STRENGTH/SEQUENCE: This includes 1.5-3.0 T with T2 , T1 , diffusion-weighted imaging (DWI), and dynamic gadoxetic acid contrast-enhancement imaging sequences. ASSESSMENT: A two-trait predictor of venous invasion (TTPVI), Lei model, Lee model, and Xu model were compared. We relied on preoperative characteristics and imaging findings via four independent radiologists who were blinded to histologic results, as required by the tested tools. STATISTICAL TEST: Tests of accuracy between predicted and observed HCC-MVI rates using receiver operating characteristic (ROC) curve and decision curve analysis. The intraclass correlation coefficient (ICC) and Cronbach's alpha statistics were used to evaluate reproducibility. RESULTS: HCC-MVI was identified in 52 patients (28.4%). The average ROC curves (AUCs) for HCC-MVI predictions were 0.709-0.880, 0.714-0.828, and 0.588-0.750 for the Xu model, Lei model, and Lee model, respectively. The rates of accuracy were 60.7-81.4%, 69.9-75.9%, and 65.6-73.8%, respectively. Decision curve analyses indicated a higher benefit for the Xu and Lei models compared to the Lee model. The ICC and Cronbach's alpha index were highest in the Lei model (0.896/0.943), followed by the Xu model (0.882/0.804), and the Lee model (0.769/0.715). The TTPVI resulted in a Cronbach's alpha index of 0.606 with a sensitivity of 34.6-61.5% and a specificity of 76.3-91.6%. DATA CONCLUSION: Stratifying schemes relying on gadoxetic acid-enhanced MRI provide an additional insight into the presence of preoperative MVI. The Xu model outperformed the other models in terms of accuracy when performed by an experienced radiologist. Conversely, the Lei model outperformed the other models in terms of reproducibility. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:433-447.

Radiologic-Radiomic Machine Learning Models for Differentiation of Benign and Malignant Solid Renal Masses: Comparison With Expert-Level Radiologists.

OBJECTIVE. The objective of our study was to compare the performance of radiologicradiomic machine learning (ML) models and expert-level radiologists for differentiation of benign and malignant solid renal masses using contrast-enhanced CT examinations. MATERIALS AND METHODS. This retrospective study included a cohort of 254 renal cell carcinomas (RCCs) (190 clear cell RCCs [ccRCCs], 38 chromophobe RCCs [chrRCCs], and 26 papillary RCCs [pRCCs]), 26 fat-poor angioleiomyolipomas, and 10 oncocytomas with preoperative CT examinations. Lesions identified by four expert-level radiologists (> 3000 genitourinary CT and MRI studies) were manually segmented for radiologicradiomic analysis. Disease-specific support vector machine radiologic-radiomic ML models for classification of renal masses were trained and validated using a 10-fold cross-validation. Performance values for the expert-level radiologists and radiologic-radiomic ML models were compared using the McNemar test. RESULTS. The performance values for the four radiologists were as follows: sensitivity of 73.7-96.8% (median, 84.5%; variance, 122.7%) and specificity of 48.4-71.9% (median, 61.8%; variance, 161.6%) for differentiating ccRCCs from pRCCs and chrRCCs; sensitivity of 73.7-96.8% (median, 84.5%; variance, 122.7%) and specificity of 52.8-88.9% for differentiating ccRCCs from fat-poor angioleiomyolipomas and oncocytomas (median, 80.6%; variance, 269.1%); and sensitivity of 28.1-60.9% (median, 84.5%; variance, 122.7%) and specificity of 75.0-88.9% for differentiating pRCCs and chrRCCs from fat-poor angioleiomyolipomas and oncocytomas (median, 50.0%; variance, 191.1%). After a 10-fold cross-validation, the radiologic-radiomic ML model yielded the following performance values for differentiating ccRCCs from pRCCs and chrRCCs, ccRCCs from fat-poor angioleiomyolipomas and oncocytomas, and pRCCs and chrRCCs from fat-poor angioleiomyolipomas and oncocytomas: a sensitivity of 90.0%, 86.3%, and 73.4% and a specificity of 89.1%, 83.3%, and 91.7%, respectively. CONCLUSION. Expert-level radiologists had obviously large variances in performance for differentiating benign from malignant solid renal masses. Radiologic-radiomic ML can be a potential way to improve interreader concordance and performance.

Impaired D2 receptor-dependent dopaminergic transmission in prefrontal cortex of awake mouse model of Parkinson's disease.

The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson's disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7-/- and PARK7+/+ mice, we found that (i) PARK7-/- neurons in the frontal association cortex showed substantially higher circuit activity recorded as spontaneous somatic Ca2+ signals; (ii) both basal and evoked dopamine release remained intact, as determined by both electrochemical dopamine recordings and high performance liquid chromatography in vivo; (iii) D2 receptor expression was significantly decreased in postsynaptic frontal association cortical neurons, and the hyper-neuronal activity were rescued by D2 receptor intervention using either local pharmacology or viral D2 receptor over-expression; and (iv) PARK7-/- mice showed anxiety-like behaviours that were rescued by either local D2 receptor pharmacology or overexpression. Thus, for first time, we demonstrated a robust D2 receptor-dependent phenotype of individual neurons within the prefrontal cortex circuit in awake parkinsonian mice that linked with anxiety. Our work sheds light on early-onset phenotypes and the mechanisms underlying Parkinson's disease by imaging brain circuits in an awake mouse model.

High-accuracy optical extensometer realized by two parallel cameras and two-dimensional digital image correlation.

A conventional optical extensometer realized by a single common camera and two-dimensional digital image correlation (2D-DIC) often provides unsatisfactory strain results owing to the out-of-plane motion of the specimen. In this work, we propose an improved optical extensometer based on two parallel cameras and 2D-DIC. In the proposed extensometer, the gauge points are selected at the image centers of two cameras, which are negligibly affected by the out-of-plane translation and rotation, leading to higher accuracy of strain measurement as compared with the conventional optical extensometer. A rigid out-of-plane translation experiment and four repeated uniaxial tensile tests were conducted to verify the feasibility, reliability, and accuracy of the proposed method. Experimental results indicate that the proposed method has a strong ability to resist the effect of out-of-plane motion and experimental vibrations. Moreover, the strain measurement results obtained with the proposed method were found to be in excellent agreement with those obtained with a strain gauge, and the strain errors between them were only a few microstrains. Given that no compensation method is required, the proposed method is easy to implement with 2D-DIC and can be used for specimens of different sizes by adjusting the distance between the two cameras.

Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma.

BACKGROUND & AIMS: Microvascular invasion (MVI) impairs surgical outcomes in patients with hepatocellular carcinoma (HCC). As there is no single highly reliable factor to preoperatively predict MVI, we developed a computational approach integrating large-scale clinical and imaging modalities, especially radiomic features from contrast-enhanced CT, to predict MVI and clinical outcomes in patients with HCC. METHODS: In total, 495 surgically resected patients were retrospectively included. MVI-related radiomic scores (R-scores) were built from 7,260 radiomic features in 6 target volumes. Six R-scores, 15 clinical factors, and 12 radiographic scores were integrated into a predictive model, the radiographic-radiomic (RR) model, with multivariate logistic regression. RESULTS: Radiomics related to tumor size and intratumoral heterogeneity were the top-ranked MVI predicting features. The related R-scores showed significant differences according to MVI status (p <0.001). Regression analysis identified 8 MVI risk factors, including 5 radiographic features and an R-score. The R-score (odds ratio [OR] 2.34) was less important than tumor capsule (OR 5.12), tumor margin (OR4.20), and peritumoral enhancement (OR 3.03). The RR model using these predictors achieved an area under the curve (AUC) of 0.909 in training/validation and 0.889 in the test set. Progression-free survival (PFS) and overall survival (OS) were significantly different between the RR-predicted MVI-absent and MVI-present groups (median PFS: 49.5 vs. 12.9 months; median OS: 76.3 vs. 47.3 months). RR-computed MVI probability, histologic MVI, tumor size, and Edmondson-Steiner grade were independently associated with disease-specific recurrence and mortality. CONCLUSIONS: The computational approach, integrating large-scale clinico-radiologic and radiomic features, demonstrates good performance for predicting MVI and clinical outcomes. However, radiomics with current CT imaging analysis protocols do not provide statistically significant added value to radiographic scores. LAY SUMMARY: The most effective treatment for hepatocellular carcinoma (HCC) is surgical removal of the tumor but often recurrence occurs, partly due to the presence of microvascular invasion (MVI). Lacking a single highly reliable factor able to preoperatively predict MVI, we developed a computational approach to predict MVI and the long-term clinical outcome of patients with HCC. In particular, the added value of radiomics, a newly emerging form of radiography, was comprehensively investigated. This computational method can enhance the communication with the patient about the likely success of the treatment and guide clinical management, with the aim of finding drugs that reduce the risk of recurrence.

Biliary Tract Cancer at CT: A Radiomics-based Model to Predict Lymph Node Metastasis and Survival Outcomes.

Purpose To evaluate a radiomics model for predicting lymph node (LN) metastasis in biliary tract cancers (BTCs) and to determine its prognostic value for disease-specific and recurrence-free survival. Materials and Methods For this retrospective study, a radiomics model was developed on the basis of a primary cohort of 177 patients with BTC who underwent resection and LN dissection between June 2010 and December 2016. Radiomic features were extracted from portal venous CT scans. A radiomics signature was built on the basis of reproducible features by using the least absolute shrinkage and selection operator method. Multivariable logistic regression model was adopted to establish a radiomics nomogram. Nomogram performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 70 consecutive patients with BTC between January 2017 and February 2018. Results The radiomics signature, composed of three LN-status-related features, was associated with LN metastasis in primary and validation cohorts (P < .001). The radiomics nomogram that incorporated radiomics signature and CT-reported LN status showed good calibration and discrimination in primary cohort (area under the curve, 0.81) and validation cohort (area under the curve, 0.80). Patients at high risk of LN metastasis portended lower disease-specific and recurrence-free survival than did those at low risk after surgery (both P < .001). High-risk LN metastasis was an independent preoperative predictor of disease-specific survival (hazard ratio, 3.37; P < .001) and recurrence-free survival (hazard ratio, 1.98; P = .003). Conclusion A radiomics model derived from portal phase CT of the liver has good performance for predicting lymph node metastasis in biliary tract cancer and may help to improve clinical decision making. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Laghi and Voena in this issue.

A radiomics approach to predict lymph node metastasis and clinical outcome of intrahepatic cholangiocarcinoma.

OBJECTIVES: This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its prognostic value. METHODS: For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients. RESULTS: The radiomics signature comprised eight LN-status-related features and showed significant association with LN metastasis in both cohorts (p < 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both p < 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival. CONCLUSIONS: Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making. KEY POINTS: • The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup. • Prognosis of high-risk patients remains dismal after curative-intent resection. • The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery.

Disseminated histoplasmosis in an immunocompetent individual diagnosed with gastrointestinal endoscopy: a case report.

BACKGROUND: Histoplasmosis is one of the invasive fungal infections and presents with symptoms mainly in the lungs. Disseminated histoplasmosis (DH) is rare and its lesions in the gastrointestinal tract are even uncommon. The concomitant involvement of the upper and lower gastrointestinal tract has never been described in the immunocompetent individuals. CASE PRESENTATION: A 44-year-old immunocompetent Chinese man presented with fever, hepatosplenomegaly, fungal esophagitis and protuberant lesions with central depression and erosion along the mucous membrane of the colon. The patient was diagnosed as disseminated histoplasmosis by gastrointestinal endoscopy. CONCLUSIONS: Histoplasmosis should be taken caution in patients with fever and hepatosplenomegaly. Actions should be taken to avoid its disseminated infection associated high mortality.

Stretch-induced Ca2+ independent ATP release in hippocampal astrocytes.

KEY POINTS: Similar to neurons, astrocytes actively participate in synaptic transmission via releasing gliotransmitters. The Ca2+ -dependent release of gliotransmitters includes glutamate and ATP. Following an 'on-cell-like' mechanical stimulus to a single astrocyte, Ca2+ independent single, large, non-quantal, ATP release occurs. Astrocytic ATP release is inhibited by either selective antagonist treatment or genetic knockdown of P2X7 receptor channels. Our work suggests that ATP can be released from astrocytes via two independent pathways in hippocampal astrocytes; in addition to the known Ca2+ -dependent vesicular release, larger non-quantal ATP release depends on P2X7 channels following mechanical stretch. ABSTRACT: Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether and how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. By contrast, two recent studies report vesicular ATP release using more direct assays. In the present study, using patch clamped 'ATP-sniffer cells', we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an 'on-cell-like' mechanical stimulus of a single astrocyte, a Ca2+ independent single large non-quantal ATP release occurred, in contrast to the Ca2+ -dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knockdown of P2X7 receptor channels. Functional P2X7 channels were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2X7 channels in astrocytes.

Radiologic evaluation of vasculobiliary anatomy in the umbilical fissure.

BACKGROUND: Preoperative evaluation of vasculobiliary anatomy in the umbilical fissure (U-point) is pivotal for perihilar cholangiocarcinoma (PCCA) applied to right-sided hepatectomy. The purpose of our study was to review the vasculobiliary anatomy in the U-point using three-dimensional (3D) reconstruction technique, to investigate the diagnostic ability of 2D scans to evaluate anatomic variations, and to discuss its surgical implications. METHODS: A retrospective study of 159 patients with Bismuth type I, II, and IIIa PCCA, who received surgery at our institution from November 2012 to September 2016, was conducted. Anatomic structures were assessed using multidetector computed tomography (MDCT) by one hepatobiliary surgeon, whereas 3D images were reconstructed by an independent radiologist. Normal confluence pattern of left biliary system was defined as the left medial segmental bile duct (B4) joining the common trunk of segment II (B2) and segment III (B3) ducts, whereas aberrant confluence patterns were classified into 3 types: type I, triple confluence of B2, B3, and B4; type II, B2 draining into the common trunk of B3 and B4; type III, other patterns. Surgical anatomy of B4 was classified into the central, peripheral, and combined type according to its relation to the hepatic confluence. The lengths from the bile duct branch of Spiegel's lobe (B1l) to the orifice of B4 and the junction of B2 and B3 were measured on 3D images. The anatomy of left hepatic artery (LHA) was classified according to different origins and the spatial relationship related to the U-point. RESULTS: 3D reconstruction revealed that normal confluence pattern of left biliary system was observed in 71.1% (113/159) of all patients, and variant patterns were type I in 11.9% (19/159), type II in 12.6% (20/159), and type III in 4.4% (7/159). The length from B1l to the junction of B2 and B3 was 12.1 ± 3.1 mm in type I variation, which was significantly shorter than that in normal configuration (30.0 ± 6.8 mm, P < 0.001) but significantly longer than that in type II variation (9.6 ± 3.4 mm, P = 0.019). Surgical anatomy of B4: the peripheral type was most commonly seen (74.2%, 118/159), followed by central type (15.7%, 25/159) and combined type (10.1%, 16/159). The distance between the B1l and B4 was 8.4 ± 2.4 mm in central and combined type, which was significantly shorter than that in peripheral type (14.5 ± 4.1 mm, P < 0.001). A replaced or accessory LHA from the left gastric artery was present in 6 (3.8%) and 9 (5.7%) patients, respectively. LHA running along the left caudal position of U-point was present in 143 cases (89.9%), along the right cranial position of U-point in nine cases (5.7 %), and combined position in seven cases (4.4%). Interobserver agreement of two imaging modalities was almost perfect in biliary confluence pattern (kappa = 0.90; 95% confidence interval: 0.79-1.00), substantial in surgical anatomy of B4 (kappa = 0.74; 95% confidence interval: 0.62-0.86), and perfect in LHA (kappa = 1.00). CONCLUSIONS: Thoroughly understanding the imaging characters of surgical anatomy in the U-point may be benefit for preoperative evaluation of PCCA by successive review of 2D images alone, whereas 3D reconstruction technique allows detailed hepatic anatomy and individualized surgical planning for advanced cases.