简介：AbstractImportance:The process of brain development in children with developmental delay is not well known. Amide proton transfer-weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.Objective:To assess the contribution of amide proton transfer-weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).Methods:Fifty-one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1-8 months; median age: 4 months) in group A showed delayed myelination on MRI , while 21 patients (3 girls, 18 boys; age range: 12-36months; median age: 25months) in group B showed normal myelination on MRI. Fifty-one age- and sex-matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent-sample t-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.Results:For group A, the MTR values were lower in all regions (P = 0.004-0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004-0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).Interpretation:For DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

简介：AbstractBackground:Certain hemophilia patients are unable to cooperate with or afford magnetic resonance imaging (MRI) examinations. The purpose of our study was to explore the value of multislice spiral computed tomography (MSCT) in evaluating hemophilic arthropathy (HA).Methods:Thirty-eight patients with 73 joints of HA were consecutively selected from January 2016 to May 2018 for this prospective study. All 73 joints were examined by X-ray, CT, and MRI within 2 days. The MRI scores of the joints were determined by the International Prophylaxis Study Group (IPSG) standard. The CT findings were quantified according to the IPSG standard, except for cartilage injury, which was quantified by joint space narrowing using the X-ray Pettersson score. The CT and MRI scores were compared by the paired Wilcoxon signed-rank test. The correlations between the CT score of joint space narrowing and MRI score of cartilage injury and the total CT and MRI scores were analyzed by Spearman rank correlation. The kappa test was used to compare the consistency of CT and MRI scores.Results:MRI was superior to CT based on the scores for small amount of effusion (P < 0.05), synovial hypertrophy and hemosiderin deposition in the mild groups (P < 0.05). The CT and MRI scores were not significantly different for moderate and massive effusion, synovial hypertrophy, and hemosiderin deposition in the moderate and severe groups, bone erosion or cystic changes (P > 0.05), and there was a high degree of consistency between the two scores (kappa > 0.81). The consistency between the Pettersson scores of joint space narrowing on CT and the IPSG scores of cartilage injury on MRI was high (kappa = 0. 774, P < 0.05).Conclusion:The image scores of MSCT are generally consistent with MRI except for mild synovitis, which can be used as an alternative for the evaluation of HA.

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简介：AbstractAdvances in imaging for preoperative localization have propelled the widespread adoption of minimally invasive/focused parathyroidectomy in primary hyperparathyroidism. Though it is performed through a relatively small incision, studies have shown that the presence of a neck scar increases attentional bias towards the neck resulting in compromised quality of life. Transoral endoscopic parathyroidectomy vestibular approach (TOEPVA) eliminates a neck scar. While indications for TOEPVA are the same as that of minimally invasive open parathyroidectomy, confident preoperative localization of the parathyroid with a surgeon performed ultrasound along with concordant localization with SPECT CT is an essential prerequisite before offering patients this approach for parathyroidectomy. Early data has demonstrated the feasibility and safety of this approach.

简介：AbstractBackground:Applying ultrasonic imaging system during surgery requires the poring of saline, performing the measurement, and acquiring data from its display—which requires time and is highly "performer dependent," i.e., the measure is of a subjective nature. A new ultrasonic device was recently developed that overcomes most of these drawbacks and was successfully applied during tumor-in-brain neurosurgeries. The purpose of this study was to compare the two types of US devices and demonstrate their properties.Methods:The study was performed in the following stages: (i) an ex vivo experiment, where slices of the muscle and brain of a young porcine were laid one on top the other. Thicknesses and border depths were measured and compared, using the two types of US instruments. (ii) During human clinical neurosurgeries, tumor depth was compared by measuring it with both devices. (iii) Following the success of stages (i) and (ii), using solely the new US device, the tumor thickness was monitored while its resection. Correlation, Pearson’s coefficient, average, mean, and standard deviation were applied for statistical tests.Results:A high correlation was obtained for the distances of tissue borders and for their respective thicknesses. Applying these ultrasonic devices during neurosurgeries, tumor depths were monitored with high similarity (87%), which was also obtained by Pearson’s correlation coefficient (0.44). The new US device, thanks to its small footprint, its remote measurement, and the capability of monitoring intraoperatively and in real-time, provides the approach to tumor’s border before its complete resection.Conclusions:The new US device provides better accuracy than an ultrasonic imaging system; its data is objective; it enables to control the residual tumor thickness during its resection, and it is especially useful in restricted areas. These features were found of great help during a tumor-in-brain surgery and especially in the final stages of tumor’s resection.

简介：AbstractLuminescence (mostly fluorescence and phosphorescence) probes are a powerful tool widely used in the life sciences research. They can be used, for example, in the quantitative analysis of physiological parameters, visualization of different cell organelles, and measurement of drug transportation. The luminescence intensity and lifetime of these probes are among the main signals recorded and evaluated in these applications. Other reviews have discussed optical probes from the perspective of their luminescence intensity. However, the luminescence lifetime, which depends on the molecular microenvironment but not the probe concentration, is another promising metric for biological sensing and imaging applications. In this review, we aim to introduce the basic strategies of FLIM probe design. We also present applications of these probes, including sensing of intracellular pH, cation/anion concentrations, oxygen levels, biomolecule contents, and physiological parameters, as well as live-cell imaging based on luminescence lifetime. Studies based on FLIM imaging of cells or tissues with endogenous organic molecules are not included in this mini review. With the rapid development of microscopy technology for fluorescence lifetime imaging, fluorescence lifetime-based probes have shown great potential in a variety of biological applications.

简介：AbstractObjective:To test the feasibility of a real time miniature endoscope system for imaging the nasopharynx.Study design:Preclinical assessment on skull model and cadaver.Methods:A 3.5 mm miniature endoscope was fabricated and the image capture of the nasopharynx was investigated by positioning the miniature camera system at the posterior free edge of the vomer bone. Wireless real time transmission of the images and quality was tested in a skull model. Next, three nasopharyngeal surveillance miniature camera system were developed for possible clinical translation. Two prototypes were anchored on the nasal septum and the last prototype was designed using a patient self-administered surveillance process. These prototypes were tested for feasibility on both the phantom skull and cadaveric model. Risk assessments were also performed to assess risk, safety and validate the reliability of the material utilized for clinical translation.Results:Insertion and anchorage of the miniature surveillance endoscope prototypes at the vomer bone were feasible on all 3 prototypes. The quality of captured images was reasonable and miniaturized camera was responsive to pan at different angles so that the entire nasopharynx may be surveyed. Risk assessments on the material such as pull out test, breaking force analysis, finite element test and tensile strength test were reliable for possible clinical translation.Conclusions:Real time miniature endoscope system for surveillance of nasopharyngeal cancer is feasible. Clinical translation of this technology was possible but requires further refinement in enhancing image quality and wireless transmission of the captured images.

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简介：AbstractObjective:Immunotherapy is an effective tumor treatment strategy. However, its long treatment cycle limits its wide application across all cancer types. In this study, we optimized upconversion nanoparticles and manganese composite particles with a porous structure as a nanoplatform for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT), and subsequent longer-term immunotherapy.Methods:The morphology, phase, and stability were first characterized to evaluate the biocompatibility of this material. The upconversion and near infrared II luminescence properties of the material and its stimuli-response effect were assessed from the absorbance and photoluminescence spectra. Phototherapy including PDT and PTT was demonstrated in vitro and in vivo, and immunotherapy was used to enhance the phototherapy. This study was approved by the Xi’an Jiaotong University, China (approval No. XJTULAC2020-585) on April 2, 2020.Results:The nanoplatform showed good PDT and PTT effects with high upconversion luminescence, and exhibited a more sensitive glutathione response (detection limit: 55 μg/mL) using fluorescence recovery than that based on absorbance recovery, with the detection range extending up to 1.2 mg/mL. When the surface of the composite particles was modified with an anti-PD-L1 immune checkpoint inhibitor, it targeted A549 lung cancer cells. The resulting immune response enhanced the long-term anti-tumor effect of the therapy, especially in lung cancer patients with high PD-L1 expression.Conclusion:The designed composite can be simultaneously used to detect the glutathione concentration based on luminescence recovery in the tumor cells and as a theranostic nanoplatform for synergistic immuno-phototherapy when combined with an antibody.

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简介：AbstractMolecular imaging is of great significance for early diagnosis and timely treatment of cancer and disease, as well as basic medical and biological research. As personalized cancer treatment has become increasingly popular, the demand for more advanced imaging technologies has also significantly increased. Taking advantage of differences between the tumor microenvironment and normal tissue cells, tumor microenvironment-responsive or "turn-on" contrast agents have a higher signal-to-noise ratio and lower background interference compared with "turn-off" probes, which can remarkably improve the performance of tumor diagnostics. Thus, tumor microenvironment-responsive contrast agents can not only detect changes in the tumor microenvironment, but also have important significance for tumor diagnosis, prediction of invasion potential, evaluation of treatment effectiveness, planning of therapeutic regimens, and tumor prognosis. Herein, this review focuses on recent research progress of tumor microenvironment-responsive intelligent probes, and highlights future research directions of tumor microenvironment-responsive contrast agents for precision diagnostics.

简介：AbstractTumor biomarkers play important roles in tumor growth, invasion, and metastasis. Imaging of specific biomarkers will help to understand different biological activities, thereby achieving precise medicine for each head and neck squamous cell carcinoma (HNSCC) patient. Here, we describe various molecular targets and molecular imaging modalities for HNSCC imaging. An extensive search was undertaken in the PubMed database with the keywords including "HNSCC," "molecular imaging," "biomarker," and "multimodal imaging." Imaging targets in HNSCC consist of the epidermal growth factor receptor, cluster of differentiation 44 variant 6 (CD44v6), and mesenchymal-epithelial transition factor and integrins. Targeted molecular imaging modalities in HNSCC include optical imaging, ultrasound, magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. Making the most of each single imaging method, targeted multimodal imaging has a great potential in the accurate diagnosis and therapy of HNSCC. By visualizing tumor biomarkers at cellular and molecular levels in vivo, targeted molecular imaging can be used to identify specific genetic and metabolic aberrations, thereby accelerating personalized treatment development for HNSCC patients.

简介：AbstractBackground:Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer.Methods:By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hregfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD).Results:In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD.Conclusions:The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies.

简介：AbstractBackground:Due to development of magnetic resonance-based functional imaging, it is easier to detect micro-structural alterations of tumor tissues. The aim of this study was to conduct a preliminary evaluation of the correlation of non-Gaussian diffusion kurtosis imaging (DKI) parameters with expression of molecular markers (epidermal growth factor receptor [EGFR]; anaplastic lymphoma kinase [ALK]; Ki-67 protein) in patients with advanced lung adenocarcinoma, using routine diffusion-weighted imaging as the reference standard.Methods:Data from patients with primary lung adenocarcinoma diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from 2016 to 2019 were collected for retrospective analysis. The pathologic and magnetic resonance imaging data of 96 patients who met the inclusion criteria were included in this study. Specifically, the Kapp and Dapp parameters measured from the DKI model; apparent diffusion coefficient (ADC) value from the diffusion-weighted imaging model; and the EGFR, ALK, and Ki-67 biomarkers detected by immunohistochemistry and/or molecular biology techniques after biopsy or surgery were evaluated. The relations between quantitative parameters (ADC, Kapp, Dapp) and pathologic outcomes (EGFR, ALK, and Ki-67 expression) were analyzed by Spearman correlation test.Results:Of the 96 lung adenocarcinoma lesions (from 96 patients), the number of EGFR- and ALK-positive and high Ki-67 expressing lesions were 53, 12, and 83, respectively. The Kapp values were significantly higher among patients with EGFR-positive mutations (0.81 ± 0.12 vs. 0.66 ± 0.10, t = 6.41, P < 0.001), ALK rearrangement-negative (0.76 ± 0.12 vs. 0.60 ± 0.15, t = 4.09, P < 0.001), and high Ki-67 proliferative index (PI) (0.76 ± 0.12 vs. 0.58 ± 0.13, t = 4.88, P < 0.001). The Dapp values were significantly lower among patients with high Ki-67 PI (3.19 ± 0.69 μm2/ms vs. 4.20 ± 0.83 μm2/ms, t = 4.80, P < 0.001) and EGFR-positive mutations (3.11 ± 0.73 μm2/ms vs. 3.59 ± 0.77 μm2/ms, t = 3.12, P = 0.002). The differences in mean Dapp (3.73 ± 1.26 μm2/ms vs. 3.26 ± 0.68 μm2/ms, t = 1.96, P = 0.053) or ADC values ([1.34 ± 0.81] × 10-3 mm2/s vs. [1.33 ± 0.41] × 10-3 mm2/s, t = 0.07, P = 0.941) between the groups with or without ALK rearrangements were not statistically significant. The ADC values were significantly lower among patients with EGFR-positive mutation ([1.19 ± 0.37] × 10-3 mm2/s vs. [1.50 ± 0.53] × 10-3 mm2/s, t = 3.38, P = 0.001) and high Ki-67 PI ([1.28 ± 0.39] × 10-3 mm2/s vs. [1.67 ± 0.77] × 10-3 mm2/s, t = 2.88, P = 0.005). Kapp was strongly positively correlated with EGFR mutations (r = 0.844, P = 0.008), strongly positively correlated with Ki-67 PI (r = 0.882, P = 0.001), and strongly negatively correlated with ALK rearrangements (r = -0.772, P = 0.001). Dapp was moderately correlated with EGFR mutations (r = -0.650, P = 0.024) or Ki-67 PI (r = -0.734, P = 0.012). ADC was moderately correlated with Ki-67 PI (r = -0.679, P = 0.033).Conclusions:The Kapp value of DKI parameters was strongly correlated with different expression of EGFR, ALK, and Ki-67 in advanced lung adenocarcinoma. The results potentially indicate a surrogate measure of the status of different molecular markers assessed by non-invasive imaging tools.

简介：AbstractSingle-domain antibodies have the characteristics of small molecular weight, strong tissue penetration, and high affinity, and are widely used to construct molecular probes for disease diagnosis and treatment. This article reviews molecular imaging studies including positron emission tomography (PET), single-photon emission computed tomography/computed tomography (CT), PET/CT, and fluorescent imaging of molecular probes composed of single-domain antibodies against eight esophageal squamous cell carcinoma biological targets. These 8 targets are highly expressed on the membrane of esophageal squamous cell carcinoma cells and include epidermal growth factor receptor, human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2, chemokine receptor 4, chemokine receptor 7, and carcinoembryonic antigen. The current problems and solutions are also discussed to provide a reference for future design of molecular imaging probes targeting esophageal squamous cell carcinoma.

简介：AbstractObjective:To assess the value of magnetic resonance imaging (MRI) in fetal lateral ventriculomegaly diagnosed with ultrasound, and to study the relationship between the degree of isolated lateral ventriculomegaly and neonatal prognosis.Methods:The pregnancy information and outcomes of 97 cases of fetal ventriculomegaly were retrospectively reviewed in the Tianjin Central Hospital of Gynecology Obstetrics from January 2016 to December 2017. The maternal age was 18-42 years, and the fetal gestational age at diagnosis was 19+4 to 37+3 weeks. MRI and ultrasound were used to compared the diagnosis of fetal lateral ventriculomegaly and evaluated the development of the nervous system after birth.Results:Among 97 pregnancy cases, associated central nervous system malformations were observed in 36 cases on ultrasound or ultrasound + MRI. Central nervous system malformations were diagnosed with ultrasound in 15 cases (15/36, 41.7%) and with ultrasound + MRI in 25 cases (25/36, 69.4%). Pearson χ2 test was used to compare the detection rates between the groups, and the difference was statistically significant (P < 0.05). We followed up 61 cases of isolated lateral ventriculomegaly for 1-3 years after birth. According to the width of the lateral ventricle of the fetus in middle pregnancy, the subjects were grouped as follows: mild 33 cases (lateral ventricle width 10.0-12.0 mm), moderate 23 cases (lateral ventricle width 12.1-15.0 mm), and severe 5 cases (lateral ventricle width >15.0 mm). The rate of normal growth and development in the mild group was 90.9% (30/33), that in the moderate group was 69.6% (16/23), and that in the severe group was 40.0% (2/5), and the difference between groups was statistically significant (P < 0.05).Conclusion:Ultrasound combined with MRI can detect more central nervous system malformations, and the degree of isolated lateral ventriculomegaly is closely related to fetal prognosis.

简介：AbstractBackground:Renal cell carcinoma (RCC) has the propensity to lead to venous tumor thrombus (VTT). Nephrectomy with tumor thrombectomy is an effective treatment option but is a technically challenging surgical procedure that is accompanied by a high rate of complications. The aims of this study were to investigate pre-operative imaging parameters for the assessment of inferior vena cava (IVC) wall invasion due to a tumor thrombus in patients with RCC and to identify predictors from the intra-operative findings.Methods:Clinical and imaging data were collected from 110 patients who underwent nephrectomy with IVC tumor thrombectomy (levels I-IV) for RCC and IVC tumor thrombus at the Peking University Third Hospital between May 2015 and March 2018. Univariable and multivariable logistic regression and receiver operating characteristic curves were used to assess the correlations between pre-operative imaging features and intra-operative macroscopic invasions of the IVC wall by tumor thrombus.Results:Among the 110 patients, 41 underwent partial or segmental resection of IVC. There were univariate associations of pre-operative imaging parameters that could be used to predict the need for IVC resection, including those of the Mayo classification, maximum anterior-posterior (AP) diameter of the renal vein at the renal vein ostium (RVo), maximum AP diameter of the VTT at the RVo and IVC occlusion. For the multivariable analysis, the AP diameter of the VTT at the RVo and IVC occlusion were associated with a significantly increased risk of invasion of the IVC wall by tumor thrombus. The optimum imaging thresholds included an AP diameter of the VTT at the RVo larger than 17.0 mm and the presence of IVC occlusion, with which we predicted invasions of the IVC wall requiring IVC resection. The probabilities of intra-operative IVC resection for patients without both independent factors, with an AP diameter of the VTT at the RVo larger than 17.0 mm, with IVC occlusion, and with both concurrent factors were 5%, 23%, 56%, and 66%, respectively.Conclusion:An increase in the AP VTT diameter at the RVo and the presence of complete occlusion of the IVC are independent risk factors for a high probability of IVC wall invasion by tumor thrombus.

简介：AbstractObjective:In order to study the important role and molecular mechanism of Brevinin-2 family antimicrobial peptide Brevinin-2ISb in methicillin-resistant Staphylococcus aureus (MRSA) infection of Caenorhabditis (C.) elegans, and to find the optimal therapeutic concentration of Brevinin-2ISb.Methods:By using a C. elegans model and MRSA infection modelto study the therapeutic effect of different concentrations of Brevinin-2ISb on C. elegans. Real-time PCR was used for investigating the effect of Brevinin-2ISb on the downstream gene expression of DAF-2/DAF-16 innate immune pathway and the major virulence factor gene expression of MRSA. With protein activity tests to study the inhibitory effect of Brevinin-2ISb on MRSA virulence factor protein activity. Finally, laser confocal imaging was carried out to observe real-time expression and distribution of downstream antimicrobial proteins to further prove the effect of Brevinin-2ISb on the activation of DAF-2/DAF-16 pathway by in vivo imaging. All animal study procedures were approved by the Academic Committee at Xidian University and Xi’an Jiaotong University Animal Care and Use Committee, China (approval No. JGC201207) on July 15, 2017.Results:Host immunity was largely enhanced by Brevinin-2ISb, and the expression of staphylococcal enterotoxin genes, as well as virulence factors, was suppressed by Brevinin-2ISb. Indeed, the expression of many C. elegans innate immune genes, including lys-7, spp-1, K05D8.5 and C29F3.7, was induced by Brevinin-2ISb. In particular, robust, sustained expression of the antibacterial gene lys-7 was observed after Brevinin-2ISb treatment, resulting in increased protein levels. These effects correlated with a reduction in the MRSA-mediated death of the C. elegans host. Low concentrations of Brevinin-2ISb exhibited very low hemolytic activity, and may play a positive role in host innate immunity. Specifically, activation of the DAF-2/DAF-16 pathway appears to be essential for immune activation in C. elegans treated with Brevinin-2ISb. Based on the evolutionary conservation of innate immune pathways, our results suggest that Brevinin-2ISb not only has strong antibacterial activity, but may also enhance the innate immune response in humans. This study demonstrates that Brevinin-2ISb-related peptides are potential candidates for the development of novel anti-inflammatory or anti-microbial drugs.Conclusion:Antimicrobial peptide Brevinin-2ISb effectively inhibits MRSA at low concentration. This antimicrobial peptide can prolong the life of MRSA-infected C. elegans, has very low hemolytic activity and inhibits the activity and expression of various MRSA virulence factors. More importantly, Brevinin-2ISb activated the expression of antimicrobial genes downstream of DAF-2/DAF-16, which enhanced the MRSA resistance of C. elegans. This peptide could be used as the basis for developing new drugs to replace antibiotics.