Quantitative Assessment of Synovial Vascularity Using Contrast-Enhanced Power Doppler Ultrasonography: Correlation with Histologic Findings and MR Imaging Findings in Arthritic Rabbit Knee Model

OBJECTIVE: To validate contrast-enhanced power Doppler ultrasonography (PD US) for the evaluation of synovial vascularity in an arthritic rabbit knee model in correlation with MR and histological findings.0aMATERIALS AND METHODS: Power Doppler ultrasonography was performed for carrageenin-induced arthritic left knee and control right knee of 13 rabbits, first without and then with sonic contrast agent enhancement (Levovist, Schering, Berlin Germany), followed by gadolinium-enhanced MR imaging. Synovial vascularity was quantitatively assessed by calculating the color pixel area in power Doppler sonography using a computer-aided image analysis program and by grading the enhancement on MR images: grade 1, enhancement of knee joint is less than one-third of the area; grade 2, one-third to two-thirds enhancement; and grade 3, more than two-thirds enhancement. Microvessel density (MVD) was measured on slides stained immunohistochemically for CD31 antigen for histological assessment.0aRESULTS: The mean area of color pixels in PD US changed from 4.37 to 16.42 mm2 in the arthritic knee after enhancement (p 0.05).0aCONCLUSION: Sonic contrast-enhanced PD US improves the visualization of synovial vascularity and allows quantitative measurement in experimentally induced rabbit arthritic knees.ope

The Effectiveness of Ferritin as a Contrast Agent for Cell Tracking MRI in Mouse Cancer Models

Purpose: We aimed to investigate the effectiveness of ferritin as a contrast agent and a potential reporter gene for tracking tumor cells or macrophages in mouse cancer models. Materials and methods: Adenoviral human ferritin heavy chain (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images were acquired before and daily for up to 6 days after the intracranial injection of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and every two days after intravenous injection of ferritin-labeled macrophages. The contrast effect of ferritin in vitro was measured by MR imaging of cell pellets. MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted (T2*w) fast low angle shot sequence. Results: Cell pellet imaging of Ad-hFTH in vitro showed a strong negatively enhanced contrast in T2w and T2*w images, presenting with darker signal intensity in high concentrations of Fe. T2w images of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity around or within the Ad-hFTH tumor, which was distinct with time and apparent in T2*w images. After injection of ferritin-labeled macrophages, negative contrast enhancement was identified within the tumor. Conclusion: Ferritin could be a good candidate as an endogenous MR contrast agent and a potential reporter gene that is capable of maintaining cell labeling stability and cellular safety.ope

Learning Radiologist’s Step-by-Step Skill for Cervical Spinal Injury Examination: Line Drawing, Prevertebral Soft Tissue Thickness Measurement, and Swelling Detection

Radiologists examine lateral view radiographs of the cervical spine to determine the presence of cervical spinal injury. In this paper, we demonstrate that an artificial intelligence neural network can learn the steps employed by a radiologist when examining these radiographs for possible injury. We deconstructed the decision-making strategy into three steps: line drawing, prevertebral soft tissue thickness (PSTT) measurement, and swelling detection. After training neural networks to be guided by the radiologist's intermediate labels, the networks successfully performed comparable line drawings to those of the radiologists, and subsequent PSTT measurement and swelling detection were successful. Quantitative comparison of PSTT measurements between our proposed method and radiologists showed a high correlation (r = 0.8663, p <; 0.05, and intraclass correlation coefficient = 0.9283 at the C2 level; r = 0.7720, p <; 0.05, and intraclass correlation coefficient = 0.8667 at the C6 level). Using the radiologist's diagnosis as the reference point, the sensitivity, specificity, and accuracy of swelling detection by our proposed method were 100%, 98.37%, and 98.48, respectively. We conclude that our neural networks successfully learned the sequence of skills used by radiologists when interpreting radiographs for injury of the cervical spine.ope

A systematic study of core size and coating thickness on manganese-doped nanocrystals for high T2 relaxivity as magnetic resonance contrast agent

We describe a systematic study of coating thickness and their effect on different core sizes for the optimized preparation of highly sensitive manganese-doped magnetic nanocrystals (MnMNCs) to be served as magnetic resonance (MR) contrast agent. From these efforts, MnMNCs with 12 nm core and DA-PEG2k coating demonstrated that T2 relaxivity (r2) was increased by 7.29-fold (r2 value: 452 mM−1 s−1) compare to conventional iron oxide (CLIO) and remarkable colloidal stability in various physiological conditions. Further in vitro cellular MR imaging results showed that MnMNC-PEGs were biocompatible and well suited for medical applications. This study will provide a useful synthetic strategy for the development of highly effective MR contrast agents.ope

Cancer -Targeted MR Molecular Imaging

Magnetic resonance (MR) imaging has been widely used in the clinic because of the benefit of high spatial and temporal resolution, and the excellent anatomical tissue contrast. Cancer-targeted MR molecular imaging comprises 3 major components: a relevant molecular target which is specifically highly expressed on the membrane of the cancer cell; a target specific imaging probe which is composed of superparamagnetic iron oxide nanoparticle coreconjugated target specific ligand such as antibody, peptide, and molecules; MR imaging hardware and software which are sensitive to the imaging probe. Among the various molecular targets, HER2/neu receptor antibody, folic acid, and arginine-glycine-aspartic acid (RGD) are well known targeting ligands. The sensitivity of the cancer-targeted MR imaging is affected by the magnetic susceptibility of the T2 contrast agent, resolution of the image, targeting efficiency of the imaging probe, and image acquisition pulse sequence. Recently, successful cancer-targeted MR imaging with T1 contrast agent and cancer-specific molecular MR imaging using innate contrast of the cancer cell by chemical exchange phenomenon without using the imaging probe has been introduced. Cancer-targeted MR molecuar imaging is a robust diagnostic method to detect cancer at the cellular stage of the cancer development and it would help improve early detection rate of the cancer.ope

Clinical Feasibility of Synthetic Magnetic Resonance Imaging in the Diagnosis of Internal Derangements of the Knee

Objective: To evaluate the feasibility of synthetic magnetic resonance imaging (MRI) compared to conventional MRI for the diagnosis of internal derangements of the knee at 3T. Materials and Methods: Following Institutional Review Board approval, image sets of conventional and synthetic MRI in 39 patients were included. Two musculoskeletal radiologists compared the image sets and qualitatively analyzed the images. Subjective image quality was assessed using a four-grade scale. Interobserver agreement and intersequence agreement between conventional and synthetic images for cartilage lesions, tears of the cruciate ligament, and tears of the meniscus were independently assessed using Kappa statistics. In patients who underwent arthroscopy (n = 8), the sensitivity, specificity, and accuracy for evaluated internal structures were calculated using arthroscopic findings as the gold standard. Results: There was no statistically significant difference in image quality (p = 0.90). Interobserver agreement (kappa = 0.649- 0.981) and intersequence agreement (kappa = 0.794-0.938) were nearly perfect for all evaluated structures. The sensitivity, specificity, and accuracy for detecting cartilage lesions (sensitivity, 63.6% vs. 54.6-63.6%; specificity, 91.9% vs. 91.9%; accuracy, 83.3-85.4% vs. 83.3-85.4%) and tears of the cruciate ligament (sensitivity, specificity, accuracy, 100% vs. 100%) and meniscus (sensitivity, 50.0-62.5% vs. 62.5%; specificity, 100% vs. 87.5-100%; accuracy, 83.3-85.4% vs. 83.3-85.4%) were similar between the two MRI methods. Conclusion: Conventional and synthetic MRI showed substantial to almost perfect degree of agreement for the assessment of internal derangement of knee joints. Synthetic MRI may be feasible in the diagnosis of internal derangements of the knee.ope

Self-labeled magneto nanoprobes using tri-aminated polysorbate 80 for detection of human mesenchymal stem cells

ope

Quantitative T2 Mapping of Knee Cartilage: Comparison between the Synthetic MR Imaging and the CPMG Sequence

The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitative MRI (QRAPMASTER) sequence for the quantitative assessment of knee cartilage. The T2 values from the phantom study showed excellent correlation between the two techniques (r2 = 0.998). The cartilage T2 values exhibited strong correlations (r2 = 0.867-0.982). Quantitative MRI (qMRI) T2 mapping can be used as an alternative to multi-echo T2 mapping, with relatively short scan time.ope

Thiolated dextran-coated gold nanorods for photothermal ablation of inflammatory macrophages

Thiolated dextran-coated gold nanorods (DEX-GNRs) were synthesized for targeted delivery to inflammatory macrophages and their photothermal ablation under near-infrared (NIR) light irradiation. Successful synthesis of DEX-GNRs was achieved using thiolated dextran, generated by applying mercaptopropionic acid to transform a hydroxyl group of dextran into a thiol group which has strong binding affinity with surfaces of GNRs. We confirmed both the existence of a thiol group in the functionalized dextran using Ellman's reagent in a thiol group assay and the characteristic band of DEX-GNRs using FT-IR spectrum. Furthermore, a cellular uptake study revealed that dextran showed a superior ability to bind the GNRs surface against macrophages compared to those of PEGylated GNRs with various molecular weights of polyethyleneglycol (PEG). Consequently, an in vitro photothermal irradiation experiment using NIR light indicated that DEX-GNRs exhibited a significant cell-killing efficacy, even with a lower concentration of Au and a low-power light sourceope

Effects for Sequential Treatment of siAkt and Paclitaxel on Gastric Cancer Cell Lines

Real-time screening of cellular response on the drugs could provide valuable insights for the early detection of therapeutic efficiency and the evaluation of disease progression. Cancer cells have the ability to vary widely in response to stress in a manner to adjust the signaling pathway to promote the survival or having a resistance to stimulation. Cell-based label-free technologies using electronic impedance sensor have strategies for constructing the signature profiles of each cells. To achieve exquisite sensitivity to substantially change of live-cell response have an important role that predict the potential of therapeutic effects. In this study, we use an impedance-based real-time cell analysis system to investigate dynamic phenotypes of cells described as a cellular index value. We show that gastric cancer cells generated characteristic kinetic patterns that corresponded to the treatment order of therapeutics. The kinetic feature of the cells offers insightful information that cannot be acquired from a conventional single end-point assay. Furthermore, we employ a 'sequential treatment strategy' to increase cytotoxic effects with minimizing the use of chemotherapeutics. Specifically, treatment of paclitaxel (PTX) after down-regulating Akt gene expression using RNAi reduces the cell proliferation and increases apoptosis. We propose that the sequential treatment may exhibit more effective approach rather than traditional combination therapy. Moreover, the dynamic monitoring of cell-drug interaction enables us to obtain a better understanding of the temporal effects in vitroope