Self-evolving persistent luminescence nanoprobes for autofluorescence-free ratiometric imaging and on-demand enhanced chemodynamic therapy of pulmonary metastatic tumors.

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.

Responsive nanoplatform for persistent luminescence "turn-on" imaging and "on-demand" synergistic therapy of bacterial infection.

Multifunctional nanotheranostic platforms are emerging for the treatment of bacterial infections. Uncontrollable drug release and poor response in target location leads to inefficient therapy and failure to offer timely antibacterial monitoring. Here, we report a multifunctional nanoplatform that can be triggered by the bacterial microenvironment for effective bacterial killing and high-sensitive persistent luminescence (PL) "turn-on" imaging. Hyaluronic acid (HA) is grafted on the surface of mesoporous silica-coated persistent luminescence nanoparticles (PLNPs@MSN) loaded with cinnamaldehyde (CA). Further in situ growth of MnO2 shells gives PLNPs@MSN@CA-HA-MnO2 (PMC-HA-MnO2). MnO2 shell of PMC-HA-MnO2 can be reduced to Mn2+ by the H2O2 in the bacterial microenvironment to trigger persistent luminescence (PL) "turn-on" imaging along with chemodynamic therapy (CDT). Meanwhile, HA can response to bacterially secreted hyaluronidase to make the packaged CA release controllable and "on-demand". Consequently, PMC-HA-MnO2 enables effective response to bacterial-infected region, ensuring high-sensitive "turn-on" imaging, synergistic CDT, accurate targeting and "on-demand" CA release to give great antibacterial effect. This nanoplatform has great potential for the diagnosis and treatment of multidrug-resistant bacterial infection with high specificity and efficiency.

Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer.

OBJECTIVES: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. METHODS: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. RESULTS: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n=128) were retraction phenomenon (odds ratio [OR]=10.188), post-acoustic shadowing (OR=5.112), and echogenic halo (OR=3.263, P<0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n=39) were calcifications (OR=6.210), absence of retraction phenomenon (OR=4.375), non-mass lesions (OR=4.286, P<0.001), absence of echogenic halo (OR=3.851, P=0.035), and post-acoustic enhancement (OR=3.641, P=0.008). The predictors for the Triple-Negative subtype (n=47) were absence of retraction phenomenon (OR=5.884), post-acoustic enhancement (OR=5.255, P<0.001), absence of echogenic halo (OR=4.138, P=0.002), and absence of calcifications (OR=3.363, P=0.001). Predictors for the Luminal-B subtype (n=89) had a relatively lower association (OR≤2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for the Luminal-A subtype (OR=9.063, P<0.001) when present and for the Triple-Negative subtype (OR=4.875, P<0.001) when absent. CONCLUSIONS: ABVS imaging features, especially retraction phenomenon, have a strong correlation with the molecular subtypes, expanding the scope of ultrasound in identifying breast cancer subtypes with confidence.

Quantitative evaluation of contrast-enhanced ultrasound for differentiation of renal cell carcinoma subtypes and angiomyolipoma.

PURPOSE: To investigate the value of quantitative parameters of contrast-enhanced ultrasound (CEUS) in the differentiation of subtypes of renal cell carcinoma (RCC) and angiomyolipoma (AML). METHODS: The quantitative characteristics of 341 RCCs and 88 AMLs were analyzed with quantitative software (SonoLiver). Quantitative analysis was conducted in the whole tumor (ROItumor) and the maximum enhanced area of the tumor (ROImax), acquiring the parameters of maximum intensity (IMAX), rise time (RT), time to peak (TTP), mean transit time (mTT), and area under the curve (AUC), were derived and analyzed. The difference values between ROImax and normal renal cortex (ΔPar.s, including ΔIMAX, ΔRT, ΔTTP, ΔmTT, ΔAUC) were compared among renal histotypes. RESULTS: All time-related parameters (including RT, TTP and mTT) of ROImax were shorter than the corresponding parameters of ROItumor in RCC subtypes (all p<0.05), but made no statistical difference in AMLs (all p>0.05). There were significant differences of all ΔPar.s among RCC subtypes and AML (all p<0.01). ΔIMAX and ΔAUC showed the trend that ccRCC>AML>pRCC=chRCC. ΔTTP showed AML=pRCC=chRCC>ccRCC, ΔRT and ΔmTT showed AML>pRCC=chRCC=ccRCC. ΔmTT could distinguish RCC from AML with the area under the ROC curve (AUC) of 0.86. The AUC of ΔIMAX and ΔAUC was 0.89 and 0.92 vs 0.85 and 0.85 for discriminating between pRCC (or chRCC) and AML vs ccRCC and AML. CONCLUSIONS: Quantitative analysis of CEUS is a useful modality in AML and RCC subtypes' differentiation, by using ΔmTT, ΔIMAX and ΔAUC.

Differentiation of subtypes of renal cell carcinoma with contrast-enhanced ultrasonography.

We aimed to assess the difference of enhancement patterns among the three RCC subtypes with contrast-enhanced ultrasound (CEUS). Two hundreds cases of pathologically proved clear cell renal cell carcinomas (ccRCC), 58 papillary renal cell carcinomas (pRCC) and 51 chromophobe renal cell carcinomas (chRCC) underwent preoperative conventional ultrasound and CEUS. The wash-in and wash-out pattern, peak enhancement degree and homogeneity, and the presence of pseudocapsule were evaluated by two blinded observers respectively. The interreader agreement in the characterization of CEUS features between two observers was good (κ  = 0.649-0.775). Compared with pRCCs and chRCCs, ccRCCs demonstrated higher frequency of simultaneous wash-in pattern, hyperenhancement and heterogeneity with necrotic areas. Most pRCCs and chRCCs manifested hypoenhancement, homogeneity, fast wash-out and presence of pseudocapsule. The only difference we obtained between pRCC and chRCC was the wash-in pattern, with slow wash-in in pRCC and simultaneous wash-in in chRCC. In small lesions with long diameter≤3 cm, the majority of the three subtypes of RCC showed homogeneous enhancement and there was no difference among them. CEUS was a useful method to preoperatively differentiate the ccRCC from non-ccRCC subtypes. There were no distinguishing features identifid on CEUS that allowed reliable differentiation of pRCC from chRCC.

Comparison of retraction phenomenon and BI-RADS-US descriptors in differentiating benign and malignant breast masses using an automated breast volume scanner.

OBJECTIVE: To compare the diagnostic values of retraction phenomenon in the coronal planes and descriptors in the Breast Imaging Reporting and Data System-Ultrasound (BI-RADS-US) lexicon in differentiating benign and malignant breast masses using an automated breast volume scanner (ABVS). MATERIALS AND METHODS: Two hundred and eight female patients with 237 pathologically proven breast masses (120 benign and 117 malignant) were included in this study. ABVS was performed for each mass after preoperative localization by conventional ultrasonography (US). Multivariate logistic regression analysis was performed to assess independent variables for malignancy prediction. Diagnostic performance was evaluated through the receiver operating characteristic (ROC) curve analysis. RESULTS: Retraction phenomenon (odds ratio [OR]: 76.70; 95% confidence interval [CI]: 12.55, 468.70; P<0.001) was the strongest independent predictor for malignant masses, followed by microlobulated margins (OR: 55.87; 95% CI: 12.56, 248.44; P<0.001), angular margins (OR: 36.44; 95% CI: 4.55, 292.06; P=0.001), calcifications (OR: 5.53; 95% CI: 1.34, 22.88; P=0.018,) and patient age (OR: 1.10; 95% CI: 1.03, 1.17; P=0.004). Mass shape, orientation, echo pattern, indistinct margins, spiculated margins, and mass size were not significantly associated with breast malignancy. Area under the ROC curve (Az) for microlobulated margins and retraction phenomenon was higher than that for other significant independent predictors. Az, sensitivity, and specificity were 0.877 (95% CI: 0.829, 0.926) and 0.838 (95% CI: 0.783, 0.892), 82.9% and 70.1%, and 92.5% and 98.3%, respectively, for microlobulated margins and retraction phenomenon. CONCLUSIONS: Retraction phenomenon and microlobulated margins have high diagnostic values in the differentiation of benign and malignant breast masses using an ABVS.

The value of contrast-enhanced ultrasound (CEUS) in detecting minute renal cell carcinoma.

UNLABELLED: To investigate the value of contrast-enhanced ultrasound (CEUS) in the detection of minute renal cell carcinoma (MRCC) compared to conventional ultrasound (US) and contrast-enhanced computed tomography (CECT). METHODS: Thirty-eight consecutive patients with 38 histopathologically proven MRCCs (≦15 mm) were enrolled in our study. CEUS and CECT were available in 38 and 24 patients, respectively. The features of CEUS were evaluated and compared to conventional ultrasound (US) and CECT. RESULTS: Ten (26.3%) tumors could not be detected by conventional US, while all tumors were detected by CEUS. The features of tumor border, blood flow, and echogenicity had significant difference between conventional US and CEUS (p=0.000, p=0.003, and p=0.012, respectively). The score of visibility of tumors by CEUS was significant higher than that of conventional US. The sensitivity, specificity, and accuracy of conventional US and CEUS in evaluating tumor necrosis were 42.9%, 50%, and 47.4% vs. 85.7%, 95.8%, and 92.1%, respectively. The enhancement features of MRCC including tumor vascularization, homogeneity, and border had no significant difference between CEUS and CECT (all p>0.05). On CEUS, synchronous-in (89.5%), hypervascular (84.2%), and fast-out (71.1%) were the most commonly observed enhancement characteristics for MRCC. CONCLUSION: CEUS performs better in detecting MRCC than conventional US, and it has the same capabilities in reflecting the enhanced features of MRCC as CECT.

Contrast-enhanced ultrasonography for evaluation of cystic renal mass: in comparison to contrast-enhanced CT and conventional ultrasound.

PURPOSE: To assess the value of contrast-enhanced ultrasonography (CEUS) in evaluating cystic renal lesions compared with conventional ultrasound (US) and contrast-enhanced computed tomography (CECT). METHODS: One hundred and three patients with complex cystic renal masses underwent preoperative US and CEUS, among which 70 conducted CECT at our institution. The images were analyzed with the number of septa, septa and wall thickness and the presence of solid component, and final diagnosis was made. RESULTS: In malignancies, CEUS demonstrated more septa, thicker wall or septa, and more solid components than US and CECT. CEUS permitted categorization of 51.7% (30/58) and 28.6% (10/35) of malignant tumors in higher grade than by US and CECT, respectively. In benign lesions, CEUS detected more septa than CECT and correctly diagnosed benign cysts which appeared as solid lesions in US. CEUS permitted downgrading of 71.1% (32/45) and 17.1% (6/35) of benign lesions compared to US and CECT. The diagnostic performance of CEUS was better than US for benign cystic lesions. The phenomenon that solid-like component by US did not enhance by CEUS was a strong predictor of benign disease, with a positive predictive value (PPV) of 100%. Enhancement of solid, soft tissue by CEUS was highly predictive of malignancy, with a PPV of 100%. CONCLUSIONS: CEUS was superior to US and CECT in visualizing the number of septa septa and wall thickness, and the presence of solid component of cystic renal lesions. CEUS may play a similar role to CECT in the diagnosis of renal cystic lesions, and better than US.