A dynamic online nomogram predicting prostate cancer short-term prognosis based on 18F-PSMA-1007 PET/CT of periprostatic adipose tissue: a multicenter study.

BACKGROUND: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT. METHODS: Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA. RESULTS: The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78-0.91), 0.77 (95% CI: 0.62-0.91) and 0.84 (95% CI: 0.70-0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram. CONCLUSION: The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.

Multimodal radiomics based on 18F-Prostate-specific membrane antigen-1007 PET/CT and multiparametric MRI for prostate cancer extracapsular extension prediction.

OBJECTIVES: To compare the performance of the multiparametric magnetic resonance imaging (mpMRI) radiomics and 18F-Prostate-specific membrane antigen (PSMA)-1007 PET/CT radiomics model in diagnosing extracapsular extension (EPE) in prostate cancer (PCa), and to evaluate the performance of a multimodal radiomics model combining mpMRI and PET/CT in predicting EPE. METHODS: We included 197 patients with PCa who underwent preoperative mpMRI and PET/CT before surgery. mpMRI and PET/CT images were segmented to delineate the regions of interest and extract radiomics features. PET/CT, mpMRI, and multimodal radiomics models were constructed based on maximum correlation, minimum redundancy, and logistic regression analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and indices derived from the confusion matrix. RESULTS: AUC values for the mpMRI, PET/CT, and multimodal radiomics models were 0.85 (95% CI, 0.78-0.90), 0.73 (0.64-0.80), and 0.83 (0.75-0.89), respectively, in the training cohort and 0.74 (0.61-0.85), 0.62 (0.48-0.74), and 0.77 (0.64-0.87), respectively, in the testing cohort. The net reclassification improvement demonstrated that the mpMRI radiomics model outperformed the PET/CT one in predicting EPE, with better clinical benefits. The multimodal radiomics model performed better than the single PET/CT radiomics model (P < .05). CONCLUSION: The mpMRI and 18F-PSMA-PET/CT combination enhanced the predictive power of EPE in patients with PCa. The multimodal radiomics model will become a reliable and robust tool to assist urologists and radiologists in making preoperative decisions. ADVANCES IN KNOWLEDGE: This study presents the first application of multimodal radiomics based on PET/CT and MRI for predicting EPE.

Radiomics based on machine learning algorithms could predict prognosis and postoperative chemotherapy benefits of patients with gastric cancer: a retrospective cohort study.

Background: Traditional clinical characteristics have certain limitations in evaluating cancer prognosis. The radiomics features provide information on tumor morphology, tissue texture, and hemodynamics, which can accurately reflect personalized predictions. This study investigated the clinical value of radiomics features on contrast-enhanced computed tomography (CT) images in predicting prognosis and postoperative chemotherapy benefits for patients with gastric cancer (GC). Methods: For this study, 171 GC patients who underwent radical gastrectomy and pathology confirmation of the malignancy at the First Affiliated Hospital of Wenzhou Medical University were retrospectively enrolled. The general information, pathological characteristics, and postoperative chemotherapy information were collected. Patients were also monitored through telephone interviews or outpatient treatment. GC patients were randomly divided into the developing cohort (n=120) and validation cohort (n=51). The intra-tumor areas of interest inside the tumors were delineated, and 1,218 radiomics features were extracted. The optimal radiomics risk score (RRS) was constructed using 8 machine learning algorithms and 29 algorithm combinations. Furthermore, a radiomics nomogram that included clinicopathological characteristics was constructed and validated through univariate and multivariate Cox analyses. Results: Eleven prognosis-related features were selected, and an RRS was constructed. Kaplan-Meier curve analysis showed that the RRS had a high prognostic ability in the developing and validation cohorts (log-rank P<0.01). The RRS was higher in patients with a larger tumor size (≥3 cm), higher Charlson score (≥2), and higher clinical stage (Stages III and IV) (all P<0.001). Furthermore, GC patients with a higher RRS significantly benefited from postoperative chemotherapy. The results of univariate and multivariate Cox regression analyses demonstrated that the RRS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) (P<0.001). A visual nomogram was established based on the significant factors in multivariate Cox analysis (P<0.05). The C-index was 0.835 (0.793-0.877) for OS and 0.733 (0.677-0.789) for DFS in the developing cohort. The calibration curve also showed that the nomogram had good agreement. Conclusions: A nomogram that combines the RRS and clinicopathological characteristics could serve as a novel noninvasive preoperative prediction model with the potential to accurately predict the prognosis and chemotherapy benefits of GC patients.

Status of 18F-PSMA-1007-PET/CT compared with multiparametric MRI in preoperative evaluation of prostate cancer.

PURPOSE: Treatment of primary prostate cancer extremely depends on preoperative stage. The role of 18F-1007-PSMA-PET/CT in preoperative staging has not been well defined. Our aim was to compare the diagnostic performance of 18F-1007-PEMA-PET/CT, mpMRI, and mpMRI + PEMA-PET/CT in local progression and lymph node invasion of prostate cancer using histopathology as the gold standard. MATERIALS AND METHODS: In this retrospective study, all patients with prostate cancer who underwent mpMRI and 18F-PSMA-1007-PET/CT before operation were included. The role of preoperative imaging was evaluated by predicting the sensitivity and specificity of EPE (extraprostatic extension), SVI (seminal vesicle invasion), and lymph node invasion results. RESULTS: Ultimately, 130 patients were included in this study. In the preoperative judgment of EPE and SVI, mpMRI + PSMA-PET/CT had higher sensitivity and specificity. When predicting lymph node metastasis, PSMA-PET/CT was the best choice. The accuracy of mpMRI + PSMA-PET/CT and PSMA-PET/CT in the T and N stages, respectively, was affected by the least factors. CONCLUSIONS: Based on the combined results of mpMRI and 18F-1007-PSMA-PET/CT, the accuracy of the preoperative judgment of prostatic capsule invasion can be improved, which may be conducive to developing intra-fascial technology while ensuring no tumor-touch isolation. PSMA-PET/CT has the advantages over mpMRI alone in terms of lymph node positivity. Compared with PSMA-PET/CT alone, the combined results can improve the sensitivity, but reduce specificity. Therefore, it is recommended to focus on PSMA-PET/CT to decide whether lymph node dissection should be performed.

White matter alterations in heart-kidney imbalance insomnia and Jiao-Tai-Wan treatment: A diffusion-tensor imaging study.

Previous studies have reported changes in white matter microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on white matter tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients who were treated with placebo or Jiao-Tai-Wan, a traditional Chinese medicine commonly used to treat heart-kidney imbalance insomnia, to assess the changes in white matter tracts. Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity and fractional anisotropy of white matter between 75 heart-kidney imbalance insomnia patients and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of mean diffusivity and fractional anisotropy were also performed in 24 heart-kidney imbalance insomnia patients (8 males; 16 females; 42.5 ± 10.4 years) with Jiao-Tai-Wan and 26 heart-kidney imbalance insomnia patients (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates. Fractional anisotropy values in left corticospinal tract were increased in heart-kidney imbalance insomnia patients. Heart-kidney imbalance insomnia patients showed lower mean diffusivity and fractional anisotropy values of several white matter tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. After being treated with Jiao-Tai-Wan, heart-kidney imbalance insomnia patients showed a trend towards reduced fractional anisotropy values in the left corticospinal tract. Jiao-Tai-Wan may improve the sleep quality by reversing the structural changes of the left corticospinal tract caused by heart-kidney imbalance insomnia.

Dilated Optic Nerve Sheath Diameter Predicts Poor Outcome in Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Optic nerve sheath diameter (ONSD) enlargement occurs in patients with intracerebral hemorrhage (ICH). However, the relationship between ONSD and prognosis of ICH is uncertain. This study aimed to investigate the predictive value of ONSD on poor outcome of patients with acute spontaneous ICH. METHODS: We studied 529 consecutive patients with acute spontaneous ICH who underwent initial CT within 6 h of symptom onset between October 2016 and February 2019. The ONSDs were measured 3 mm behind the eyeball on initial CT images. Poor outcome was defined as having a Glasgow Outcome Scale (GOS) score of 1-3, and favorable outcome was defined as having a GOS score of 4-5 at discharge. RESULTS: The ONSD of the poor outcome group was significantly greater than that of the favorable outcome group (5.87 ± 0.86 vs. 5.21 ± 0.69 mm, p < 0.001). ONSD was related to hematoma volume (r = 0.475, p < 0.001). Adjusting other meaningful predictors, ONSD (OR: 2.83; 95% CI: 1.94-4.15) was associated with poor functional outcome by multivariable logistic regression analysis. Receiver operating characteristic curve showed that the ONSD improved the accuracy of ultraearly hematoma growth in the prediction of poor outcome (AUC: 0.790 vs. 0.755, p = 0.016). The multivariable logistic regression model with all the meaningful predictors showed a better predictive performance than the model without ONSD (AUC: 0.862 vs. 0.831, p = 0.001). CONCLUSIONS: The dilated ONSD measured on initial CT indicated elevated intracranial pressure and poor outcome, so appropriate intervention should be taken in time.

Astral hydrogels mimic tissue mechanics by aster-aster interpenetration.

Many soft tissues are compression-stiffening and extension-softening in response to axial strains, but common hydrogels are either inert (for ideal chains) or tissue-opposite (for semiflexible polymers). Herein, we report a class of astral hydrogels that are structurally distinct from tissues but mechanically tissue-like. Specifically, hierarchical self-assembly of amphiphilic gemini molecules produces radial asters with a common core and divergently growing, semiflexible ribbons; adjacent asters moderately interpenetrate each other via interlacement of their peripheral ribbons to form a gel network. Resembling tissues, the astral gels stiffen in compression and soften in extension with all the experimental data across different gel compositions collapsing onto a single master curve. We put forward a minimal model to reproduce the master curve quantitatively, underlying the determinant role of aster-aster interpenetration. Compression significantly expands the interpenetration region, during which the number of effective crosslinks is increased and the network strengthened, while extension does the opposite. Looking forward, we expect this unique mechanism of interpenetration to provide a fresh perspective for designing and constructing mechanically tissue-like materials.

Arc concave sign on thin-section computed tomography：A novel predictor for invasive pulmonary adenocarcinoma in pure ground-glass nodules.

OBJECTIVE: We aimed to investigate the risk factors of invasive pulmonary adenocarcinoma, especially to report and validate the use of our newly identified arc concave sign in predicting invasiveness of pure ground-glass nodules (pGGNs). METHODS: From January 2015 to August 2018, we retrospectively enrolled 302 patients with 306 pGGNs ≤ 20 mm pathologically confirmed (141 preinvasive lesions and 165 invasive lesions). Arc concave sign was defined as smooth and sunken part of the edge of the lesion on thin-section computed tomography (TSCT). The degree of arc concave sign was expressed by the arc chord distance to chord length ratio (AC-R); deep arc concave sign was defined as AC-R larger than the optimal cut-off value. Logistic regression analysis was used to identify the independent risk factors of invasiveness. RESULTS: Arc concave sign was observed in 65 of 306 pGGNs (21.2 %), and deep arc concave sign (AC-R > 0.25) were more common in invasive lesions (P = 0.008). Under microscope, interlobular septal displacements were found at tumour surface. Multivariate analysis indicated that irregular shape (OR, 3.558; CI: 1.374-9.214), presence of deep arc concave sign (OR, 3.336; CI: 1.013-10.986), the largest diameter > 10.1 mm (OR, 4.607; CI: 2.584-8.212) and maximum density > -502 HU (OR, 6.301; CI: 3.562-11.148) were significant independent risk factors of invasive lesions. CONCLUSIONS: Arc concave sign on TSCT is caused by interlobular septal displacement. The degree of arc concave sign can reflect the invasiveness of pGGNs. Invasive lesions can be effectively distinguished from preinvasive lesions by the presence of deep arc concave sign, irregular shape, the largest diameter > 10.1 mm and maximum density > -502 HU in pGGNs ≤ 20 mm.

Dynamic changes on chest CT of COVID-19 patients with solitary pulmonary lesion in initial CT.

PURPOSE: To investigate the dynamic evolution of image features of COVID-19 patients appearing as a solitary lesion at initial chest CT scan. MATERIALS AND METHODS: Twenty-two COVID-19 patients with solitary pulmonary lesion from three hospitals in China were enrolled from January 18, 2020 to March 18, 2020. The clinical feature and laboratory findings at first visit, as well as characteristics and dynamic evolution of chest CT images were analyzed. Among them, the CT score evaluation was the sum of the lung involvement in five lobes (0-5 points for each lobe, with a total score ranging from 0 to 25). RESULTS: 22 COVID-19 patients (11 males and 11 females, with an average age of 40.7 ± 10.3) developed a solitary pulmonary lesion within 4 days after the onset of symptoms, the peak time of CT score was about 11 days (with a median CT score of 6), and was discharged about 19 days. The peak of CT score was positively correlated with the peak time and the discharge time (p < 0.001, r = 0.793; p < 0.001, r = 0.715). Scan-1 (first visit): 22 cases (100%) showed GGO and one lobe was involved, CT score was 1.0/1.0 (median/IQR). Scan-2 (peak): 15 cases (68%) showed crazy-paving pattern, 19 cases (86%) showed consolidation, and 2.5 lobes were involved, CT score was 6.0/12.0. Scan-3 (before discharge): ten cases (45%) showed linear opacities, none had crazy-paving pattern, and 2.5 lobes were involved, CT score was 6.0/11.0. Scan-4 (after discharge): three cases (19%) showed linear opacities and one lobe was involved, CT score was 2.0/5.0. CONCLUSION: The chest CT features are related to the course of COVID-19 disease, and dynamic chest CT scan are helpful to monitor disease progress and patients' condition. In recovered patients with COVID-19, the positive CT manifestations were found within 4 days, lung involvement peaking at approximately 11 days, and discharged at about 19 days. The patients with more severe the lung injury was, the later the peak time appeared and the longer the recovery time was. Although the lesion was resolved over time, isolation and reexamination were required after discharge.

Risk Factors for The Growth of Residual Nodule in Surgical Patients with Adenocarcinoma Presenting as Multifocal Ground-glass Nodules.

PURPOSE: We aim to investigate the risk factors influencing the growth of residual nodule (RN) in surgical patients with adenocarcinoma presenting as multifocal ground-glass nodules (GGNs). METHOD: From January 2014 to June 2018, we enrolled 238 patients with multiple GGNs in a retrospective review. Patients were categorized into growth group 63 (26.5%), and non-growth group 175 (73.5%). The median follow-up time was 28.2 months (range, 6.3-73.0 months). To obtain the time of RN growth and find the risk factors for growth, data such as age, gender, history of smoking, history of malignancy, type of surgery, pathology and radiological characteristics were analyzed to use Kaplan-Meier method with the log-rank test and Cox regression analysis. RESULTS: The median growth time of RN was 56.0 months (95% CI, 45.0-67.0 months) in all 238 patients. Roundness (HR 4.62, 95% CI 2.20-9.68), part-solid nodule (CTR ≥ 50%) (HR 4.39, 95% CI 2.29-8.45), vascular convergence sign (HR 2.32, 95% CI 1.36-3.96) of RN, and age (HR 1.04, 95% CI 1.01-1.07) were independent predictors of further nodule growth. However, radiological characteristics and pathology of domain tumour (DT) cannot be used as indicators to predict RN growth. CONCLUSIONS: RN showed an indolent growth pattern in surgical patients with multifocal GGNs. RN with a higher roundness, presence of vascular convergence sign, more solid component, and in the elder was likely to grow. However, the growth of RN showed no association with the radiological features and pathology of DT.

Intrarenal delivery of bFGF-loaded liposome under guiding of ultrasound-targeted microbubble destruction prevent diabetic nephropathy through inhibition of inflammation.

Basic fibroblast growth factor (bFGF) has shown great therapeutic effects for diabetic nephropathy (DN). However, its clinical applications are limited due to its short half-life, low stability and poor penetration. Herein, a bFGF-loaded liposome (bFGF-lip) was constructed and combined with ultrasound-targeted microbubble destruction (UTMD) to overcome these drawbacks. bFGF-lip exhibited spherical morphology with a diameter of 171.1 ± 14.2 nm and a negative zeta potential of -5.15 ± 2.08 mV, exhibiting a sustained-release profile of bFGF. DN rat models were successfully induced by streptozotocin. After treatment with bFGF-lip + UTMD, the concentration of bFGF in kidney of DN rats was significantly enhanced in comparison with free bFGF treatment. Additionally, the morphology and the function of the kidneys were obviously recovered after bFGF-lip + UTMD treatment as shown by ultrasonography and histological analyse. The molecular mechanism was associated with the inhibition of renal inflammation. After treatment with bFGF-lip + UTMD, the activation of NF-κB was obviously reduced in the renal tissues, and downstream inflammatory mediators including TGF-ß1, MCP-1, IL-6 and IL-1ß were also down regulated. In addition, inflammation-induced cellular apoptosis of renal tubular cells was also significantly inhibited by detecting Bax, caspase-3 and Bcl-2. Therefore, bFGF-lip in combination with UTMD might be a potential strategy to reverse the progression of early DN.

Combination of coenzyme Q10-loaded liposomes with ultrasound targeted microbubbles destruction (UTMD) for early theranostics of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN. CoQ10-lip exhibited a good round morphology with a diameter of 183±1.7nm and a negative zeta potential of -25.3mV, which was capable of prolonging the release of the encapsulated CoQ10. The early DN rat models were induced by streptozotocin (STZ) and confirmed by contrast-enhanced ultrasound (CEUS) and 24-h urinary albumin. After the administration of CoQ10-lip combined with the UTMD technique to rats with early DN, the morphology and function of the kidney were evaluated by ultrasonography, histological and molecular analyses. The renal hemodynamics were significantly improved, moreover, 24-h urinary protein, and oxidative stress indexes were modulated after treatment with CoQ10-lip+UTMD indicating recovery of renal function. An elevated level of Nphs2 protein and reduced caspase 3 level indicated the preservation of podocytes and inhibition of cell apoptosis after CoQ10-lip+UTMD treatment. The molecular mechanism was associated with the upregulation of Bcl-2 and the downregulation of Bax. Moreover, the combination of CoQ10-lip and ultrasound microbubbles demonstrated a better protective effect on the damaged kidney than the other groups (free CoQ10 or CoQ10-lip+/- UTMD). Conclusively, CoQ10-lip in combination with ultrasound microbubbles might be a potential strategy to reverse the progress of early DN.