Recent advances in near-infrared II imaging technology for biological detection.

Molecular imaging technology enables us to observe the physiological or pathological processes in living tissue at the molecular level to accurately diagnose diseases at an early stage. Optical imaging can be employed to achieve the dynamic monitoring of tissue and pathological processes and has promising applications in biomedicine. The traditional first near-infrared (NIR-I) window (NIR-I, range from 700 to 900 nm) imaging technique has been available for more than two decades and has been extensively utilized in clinical diagnosis, treatment and scientific research. Compared with NIR-I, the second NIR window optical imaging (NIR-II, range from 1000 to 1700 nm) technology has low autofluorescence, a high signal-to-noise ratio, a high tissue penetration depth and a large Stokes shift. Recently, this technology has attracted significant attention and has also become a heavily researched topic in biomedicine. In this study, the optical characteristics of different fluorescence nanoprobes and the latest reports regarding the application of NIR-II nanoprobes in different biological tissues will be described. Furthermore, the existing problems and future application perspectives of NIR-II optical imaging probes will also be discussed.

Gadolinium-loaded calcium phosphate nanoparticles for magnetic resonance imaging of orthotopic hepatocarcinoma and primary hepatocellular carcinoma.

The development of magnetic resonance imaging (MRI) contrast agents with high sensitivity and good biocompatibility is of great value for the diagnosis of primary hepatocellular carcinoma (HCC). Here, a novel MRI contrast agent based on calcium phosphate (CaP) nanoparticles modified with a liver cancer cell targeting peptide A54 (A54-CaP) was fabricated. The T1-positive contrast agent Gd-DTPA was encapsulated inside the nanoparticles (A54-CaPNPs), with a mean diameter of 30 nm and a high encapsulation efficiency of 92.73%. The A54-CaPNP solution exhibited higher longitudinal relaxivity (6.07 mM-1 s-1) than that of the clinically used MRI contrast agent Gd-DTPA (3.56 mM-1 s-1). A much higher accumulation of the nanoparticles in the liver cells was observed, which was directed by the A54 targeting peptide. Furthermore, the MRI diagnostic efficiency of A54-CaPNPs was systematically investigated in an orthotopic liver cancer model and primary HCC model. In vivo MRI experiments showed that A54-CaPNPs had higher sensitivity in the BEL-7402 orthotopic liver cancer model with a more remarkable contrast enhancement and a longer imaging time compared to those without A54 modification. Moreover, the experiments on primary HCC models suggested that A54-CaPNPs showed greatly enhanced MR imaging performance in comparison with Gd-DTPA. These results suggest that A54-CaPNPs possess great potential to enable the non-invasive early diagnosis of primary HCC for timely surgical resection.

Combinational protective therapy for spinal cord injury medicated by sialic acid-driven and polyethylene glycol based micelles.

Spinal cord injury (SCI) leads to immediate disruption of neuronal membranes and loss of neurons, followed by extensive secondary injury process. Treatment of SCI still remains a tremendous challenge clinically. Minocycline could target comprehensive secondary injury via anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms. Polyethylene glycol (PEG), a known sealing agent, is able to seal the damaged cell membranes and reduce calcium influx, thereby exerting neuroprotective capacity. Here, an E-selectin-targeting sialic acid - polyethylene glycol - poly (lactic-co-glycolic acid) (SAPP) copolymer was designed for delivering hydrophobic minocycline to achieve combinational therapy of SCI. The obtained SAPP copolymer could self-assemble into micelles with critical micelle concentration being of 13.40 µg/mL, and effectively encapsulate hydrophobic minocycline. The prepared drug-loaded micelles (SAPPM) displayed sustained drug release over 72 h, which could stop microglia activation and exhibited excellent neuroprotective capacity in vitro. The SAPP micelles were efficiently accumulated in the lesion site of SCI rats via the specific binding between sialic acid and E-selectin. Due to the targeting distribution and combinational effect between PEG and minocycline, SAPPM could obviously reduce the area of lesion cavity, and realize more survival of axons and myelin sheaths from the injury, thus distinctly improving hindlimb functional recovery of SCI rats and conferring superior therapeutic effect in coparison with other groups. Our work presented an effective and safe strategy for SCI targeting therapy. Besides, neuroprotective capacity of PEG deserves further investigation on other central nervous system diseases.

Sialic Acid-Functionalized pH-Triggered Micelles for Enhanced Tumor Tissue Accumulation and Active Cellular Internalization of Orthotopic Hepatocarcinoma.

Both targeted and stimuli-sensitive drug-delivery systems (DDSs) have been developed to augment antitumor effects. However, lack of knowledge regarding tumor tissue targeting and different effects of the stimuli-sensitive DDSs in orthotropic and ectopic tumors have impeded further advances in their clinical applications. Herein, we first reported a pH-triggered micelle with sialic acid (SA)-driven targeting ability (SA-poly(ethylene glycol)-hydrazone linker-doxorubicin (DOX), SPD). The SPD micelles encapsulated with DOX (SPDD) showed sustained drug release over 48 h in response to the pH gradient in vivo, slow under physical conditions and accelerated in the acid tumor microenvironment. In addition, the SPD micelles showed 2.3-fold higher accumulation in tumors after 48 h compared to the micelles lacking the SA moiety. The overexpression of E-selectin on the inflammatory vascular endothelial cells surrounding the tumors increased the accumulation of SPD micelles in tumor tissues, whereas that on the tumor cells increased the internalization of micelles. Consequently, SPDD micelles exerted remarkable antitumor effects in both orthotopic and ectopic models. Application of SPDD micelles in the in situ model reduced the tumor volume (77.57 mm3 vs 62.13 mm3) and metastasis after treatment for 25 days. These results suggest that SA-driven targeted DDS with a pH-responsive switch has the potential to treat hepatocarcinoma effectively both ectopically and orthotopically.

Visual targeted therapy of hepatic cancer using homing peptide modified calcium phosphate nanoparticles loading doxorubicin guided by T1 weighted MRI.

Effective treatment and real-time monitoring of hepatic cancer are essential. A multifunctional calcium phosphate nanoparticles loading chemotherapeutic agent doxorubicin and magnetic resonance imaging contrast agent diethylenetriaminepentaacetic acid gadolinium (A54-CaP/Gd-DTPA/DOX) was developed for visual targeted therapy of hepatic cancer via T1-weighted MRI in real-time. A54-CaP/Gd-DTPA/DOX exhibited a higher longitudinal relaxivity (6.02 mM-1 s-1) than commercial MR contrast agent Gd-DTPA (3.3765 mM-1 s-1). The DOX release from the nanoparticles exhibited a pH dependent behavior. The cellular uptake results showed that the internalization of A54-CaP/Gd-DTPA/DOX into BEL-7402 cells was1.9-fold faster than that of HepG2 cells via A54 binding. In vivo experiments presented that A54-CaP/Gd-DTPA/DOX had higher distribution and longer retention time in tumor tissue than CaP/Gd-DTPA/DOX and free DOX, and also displayed great antitumor efficacy (95.38% tumor inhibition rate) and lower toxicity. Furthermore, the Gd-DTPA entrapped in the nanoparticles could provide T1-weighted MRI for real-time monitoring the progress of tumor treatment.

Lymphadenitis associated with cat-scratch disease simulating a neoplasm: Imaging findings with histopathological associations.

The lymphadenitis associated with cat-scratch disease (CSD) is often confused with neoplasms by a number of radiologists and clinicians, and consequently, unnecessary invasive procedures or surgeries are performed. In the present study, the contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) findings of 10 patients (6 men and 4 women) with clinically and pathologically confirmed lymphadenitis associated with CSD were retrospectively analyzed (CT in 3 patients, MRI in 6 patients, and CT and MRI in 1 patient) at The Second Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China) between January 2007 and November 2014. As a result, 17 enlarged lymph nodes were identified in 10 cases. The 5 nodes identified by CT scan exhibited relatively inhomogeneous isodensity to muscle, with patchy low density in the center. All 14 nodes identified by MRI scan exhibited homogeneous or heterogeneous isointensity to muscle or slightly increased intensity compared with that of muscle on T1-weighted images (T1WI), and homogeneous or heterogeneous hyperintensity on fat-suppressed T2WI. Following enhancement, all 17 enlarged lymph nodes associated with CSD demonstrated the following 3 different enhancement patterns: Moderate homogeneous enhancement (n=8), which was associated with histologically identified early disease stage; marked heterogeneous enhancement with no enhancement of the necrotic areas (n=4), and heterogeneous enhancement with progressively 'spoke-wheel-like' (defined as radiating enhancement from the center) enhancement of the patchy low-density area (n=1), which was associated with histologically identified intermediate disease stage; and astral low-density/hypointensity with marked enhancement (n=2) or a 'rose flower' sign (n=2), which was associated with histologically identified late disease stage. We hypothesized that the CT and MRI results of lymphadenitis in CSD may be associated with the pathological features. It may be suggested that the diagnosis of CSD may be formed when considering the characteristic CT and MRI features of astral low-density/hypointensity with marked enhancement or a 'rose flower' sign (defined as marginal petaloid enhancement) in the late disease stage, or the MRI results of homogeneous, moderate enhancement in the early disease stage, or the CT/MRI data of heterogeneous enhancement with non-enhancing area in the center in the intermediate disease stage, in solitary or multiple enlarged lymph nodes associated with general subcutaneous edema in the vicinity of the nodes on CT/MRI and with a history of cat exposure.

Contrast-enhanced multiple-phase imaging features of intrahepatic mass-forming cholangiocarcinoma and hepatocellular carcinoma with cirrhosis: A comparative study.

The intrahepatic mass-forming cholangiocarcinoma (IMCC) is frequently misdiagnosed as hepatocellular carcinoma (HCC) in patients with cirrhosis, by numerous radiologists and clinical doctors, which results in the incorrect therapeutic treatment. A retrospective case-control study was conducted, and the contrast-enhanced multiple-phase (CEMP) computed tomography (CT) and magnetic resonance imaging (MRI) findings of 22 pathologically confirmed IMCC patients and 22 HCC controls with underlying liver cirrhosis were analyzed at the present hospital, from January 2010 to December 2015. In addition, serum tests were conducted and clinical symptoms of patients evaluated. A statistical analysis revealed that the enhancement pattern, signal on MRI delayed phase (P<0.001), maximum diameter, capsule retraction, portal vein invasion, bile duct dilation and abdominal lymphadenectasis characteristics were different between IMCC and HCC patients with cirrhosis. On CEMP CT and MRI analysis, the most frequently occurring enhancement patterns of IMCC were progressive patterns (P=0.001 or P<0.001). Conversely, the most frequently occurring enhancement patterns present in HCC were the washout patterns (P<0.001). Therefore, the diagnosis of IMCC in cirrhotic patients should be verified with CEMP CT and MRI analysis for the future, to determine presence or absence of progressive and/or peripheral rim-like enhancement, a hyperintensive delayed phase with capsule retraction, portal vein invasion, bile duct dilation, abdominal lymphadenectasis and increased levels of CA199.

T2-Weighted Magnetic Resonance Imaging of Hepatic Tumor Guided by SPIO-Loaded Nanostructured Lipid Carriers and Ferritin Reporter Genes.

Nowadays, there is a high demand for supersensitive contrast agents for the early diagnostics of hepatocarcinoma. It has been recognized that accurate imaging information is able to be achieved by constructing hepatic tumor specific targeting probes, though it still faces challenges. Here, a AGKGTPSLETTP peptide (A54)-functionalized superparamagnetic iron oxide (SPIO)-loaded nanostructured lipid carrier (A54-SNLC), which can be specifically uptaken by hepatoma carcinoma cell (Bel-7402) and exhibited ultralow imaging signal intensity with varied Fe concentration on T2-weighted imaging (T2WI), was first prepared as an effective gene carrier. Then, an endogenous ferritin reporter gene for magnetic resonance imaging (MRI) with tumor-specific promoter (AFP-promoter) was designed, which can also exhibit a decrease in signal intensity on T2WI. At last, using protamine as a cationic mediator, novel ternary nanoparticle of A54-SNLC/protamine/DNA (A54-SNPD) as an active dual-target T2-weighted MRI contrast agent for imaging hepatic tumor was achieved. Owing to the synergistic effect of A54-SNLC and AFP-promoted DNA targeting with Bel-7402 cells, T2 imaging intensity values of hepatic tumors were successfully decreased via the T2 contrast enhancement of ternary nanoparticles. It is emphasized that the novel A54-SNPD ternary nanoparticle as active dual-target T2-weighted MRI contrast agent were able to greatly increase the diagnostic sensitivity and specificity of hepatic cancer.

Evaluation of the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis using 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.

Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging.

Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 µg. mL-1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.

Gastric schwannoma: CT findings and clinicopathologic correlation.

PURPOSE: The purpose of this study was to evaluate the computed tomography (CT) imaging characteristics of gastric schwannoma. METHODS: Eight cases of gastric schwannomas confirmed by surgery and pathology were retrospectively analyzed by CT. We reviewed the CT findings of gastric schwannomas for the following characteristics: tumor location, size, contour, margin, growth pattern, enhancement pattern, the presence or absence of necrosis, and perigastric lymph nodes. RESULTS: The tumors were located in the lesser curvature of gastric body (n = 5) and greater curvature of the gastric antrum (n = 3) with a median size of 4.8 cm (range 1.7-11.4 cm). Gastric schwannomas appeared as submucosal tumors with CT features of ovoid (7/8 patients), well-defined (8/8) and exophytic (4/8) or mixed (3/8) growth patterns. On dynamic CT examination, the tumors displayed homogeneous enhancement in seven cases and heterogeneous enhancement in one case. Solid parts of eight tumors demonstrated mild enhancement during the arterial phase and strengthened progressive enhancement during the venous and delayed phases. Two cases had perigastric lymph nodes. CONCLUSIONS: Gastric schwannomas typically manifested as ovoid, well-defined, exophytic, or mixed growth pattern masses on CT. Homogeneous progressive enhancement on dynamic CT is a characteristic finding of gastric schwannoma.

Epithelioid angiomyolipoma of the liver: CT and MRI features.

The purpose of our study was to retrospectively evaluate the computed tomography (CT)/magnetic resonance imaging features of epithelioid angiomyolipoma of the liver (Epi-HAML), with pathology as a reference. We reviewed the CT/MRI findings of six lesions of Epi-HAML and found absence of adipose tissue in the lesions. In addition, recognizing the imaging features of no capsule, and hypervasularity with central punctiform or filiform vessels as a characteristic enhancement may distinguish Epi-HAML from other hepatic tumors.

[Preparation and in vivo-in vitro evaluation of compound nanoparticles loaded with epirubicin hydrochloride and gadopentetate meglumine].

OBJECTIVE: To prepare and characterize the compound Epirubicin hydrochloride and Gadopentetate meglumine (Gd-DTPA) nanoparticles, and evaluate its properties from rabbits in vivo and in vitro. METHODS: The compound Epirubicin hydrochloride and Gd-DTPA nanoparticles were prepared by double emulsion-solvent evaporation method. The main effective factors were orthogonal designed. The characteristics such as drug entrapment efficiency, drug loading, and drug utilization were assayed in vitro. MR imaging effect of the VX2 rabbit hepatoma model were observed after injecting the drug-loaded nanoparticles through the hepatic artery intubation in vivo. RESULTS: The drug encapsulation efficiency of the nanoparticles, drug loading and drug utilization were 33.8% ± 3.4%, 0.225% ± 0.052%, and 69.6% ± 4.3% under the optimized prescription, respectively. The mean size of the nanoparticles was 180.6 nm, the drug release continued in 48 h with good MR imaging effect. CONCLUSIONS: Compound Epirubicin hydrochloride and Gd-DTPA Nanoparticles were in simply preparation and showed sustained drug release properties. These novel nanoparticles with detecting function could develop of epirubicin hydrochloride targeted therapy of liver cancer.

[Spiral computed tomography images of extraluminal type gastric stromal tumors].

OBJECTIVE: To evaluate the diagnostic value of spiral CT and its reconstruction techniques in the diagnosis of extraluminal type gastric stromal tumors. METHODS: The data of spiral CT performed 1 week before operation of 17 extraluminal type cases, 11 males and 6 females, aged 35.5 (13-67), from 33 patients of gastric stromal tumors proved by pathology and immunohistochemistry, were analyzed retrospectively. RESULTS: The accuracy rates of level diagnosis and qualitative diagnosis of extraluminal type gastric stromal tumor by spiral CT were 88.2% and 82.4% respectively. The main CT manifestations included: (1) extraluminal mass connected with the gastric wall, with round or lobulated margin and characteristic horn-like appearance and direct invasion, more than 5.0 cm in diameter; (2) inhomogeneous density of mass, including mild to moderate uneven enhancement in artery phase and obvious enhancement in vein and delay phase in 15 cases, and obvious enhancement in artery phase and decrease of enhancement in portal vein phases in 2 cases. (3) Irregular niches and sinus in the margins of the intraluminal masses (n = 11) and unclear border of the masses and invasion into nearby structures (n = 9); (4) connection of the tumor and stomach wall by broad boundary or failure to distinguish the tumor and stomach wall; and (5) invasion to the surrounding tissues and organs as a sign of malignant tumors. CONCLUSION: Spiral CT and its reconstruction techniques have important value in level diagnosis and qualitative diagnosis of extraluminal type gastric stromal tumors.