Nanomaterial based Magnetic Resonance Imaging of Cancer

Magnetic Resonance Imaging (MRI) is a widely used non-invasive medical tool for detection and diagnosis of cancer. In recent years, MRI has witnessed significant contributions from nanotechnology to incorporate advanced features such as multimodality of nanoparticles, therapeutic delivery, specific targeting and the optical detectability for molecular imaging. Accurate composition, right scheme of surface chemistry and properly designed structure is essential for achieving desired properties of nanomaterials such as non-fouling surface, high imaging contrast, chemical stability, target specificity and/or multimodality. This review provides an overview of the recent progress in theranostic nanomaterials in imaging and the development of nanomaterial based magnetic resonance imaging of cancer. In particular, targeted theranostics is a promising approach along with its targeting strategy in cancer treatment using MRI and multimodal imaging. We also discuss recent advances in integrin mediated targeted MRI of cancer.

Efficient generation of diffraction-limited multi-sheet pattern for biological imaging

We demonstrate a new technique to generate multiple light-sheets for fluorescence microscopy. This is possible by illuminating the cylindrical lens using multiple copies of Gaussian beams. A diffraction grating placed just before the cylindrical lens splits the incident Gaussian beam into multiple beams traveling at different angles. Subsequently, this gives rise to diffraction-limited light-sheets after the Gaussian beams pass through the combined cylindrical lens-objective sub-system. Direct measurement of field at and around the focus of objective lens shows multi-sheet pattern with an average thickness of 7.5 mu m and inter-sheet separation of 380 mu m. Employing an independent orthogonal detection sub-system, we successfully imaged fluorescently-coated yeast cells (approximate to 4 mu m) encaged in agarose gel-matrix. Such a diffraction-limited sheet-pattern equipped with dedicated detection system may find immediate applications in the field of optical microscopy and fluorescence imaging. (C) 2015 Optical Society of America

Imaging cellular signalling: many `moving tales' in MAP kinase odyssey

Cellular signalling events are at the core of every adaptive response. Signalling events link environmental changes to physiological responses, consequently allowing cellular and organismal sustenance and survival. Classical approaches to study cellular signalling have relied on a variety of cell disruptive techniques which yield limited kinetic information, while the underlying events are much more complex. In this article, we discuss how modern live cell imaging microscopy has found increasing utilization in revealing spatio temporal dynamics of various signalling pathways. Utilizing the well studied mitogen-activated protein kinase (MAPK) signalling cascade as a template, the design, construction and utilization of `mobile' (translocation proficient) biosensors, suitable for studying MAPK signalling in living cells are described in detail. Experimental setup and results obtained from these biosensors, based on different proteins involved in the MAPK signalling cascade, have been described along with the setup of a microscope optimal for live cell imaging applications. Utilizing the ability to activate or deactivate signalling pathways using defined activators and specific pharmacological inhibitors, we also show how these sensors can yield unique spatial and temporal kinetic information of signalling in living cells.

Dispersible crystalline nanobundles of YPO4 and Ln (Eu, Tb)-doped YPO4: rapid synthesis, optical properties and bio-probe applications

Undoped and Ln(3+) (Eu and Tb)-doped crystalline nanobundles of YPO4 were prepared by a facile microwave-assisted route with water as a solvent and without using any surfactant. TEM investigations reveal that the as-prepared powder consists of lenticular-shaped nanobundles (similar to 100 nm in diameter) made of very small nanorods with diameter less than 10 nm and length varying from 20 to 50 nm. Each nanorod in turn is single crystalline, as revealed by HRTEM imaging. The as-prepared nanobundles are easily dispersible in various solvents, especially water, without any surface functionalization, which is critical for various bio-probe applications like cell and tissue imaging. The Eu- and Tb-doped YPO4 nanobundles show good photoluminescence properties and were further evaluated for their use as fluorescent biolabels. Our results show that HeLa cells labelled with Eu- and Tb-doped YPO4 nanobundles show bright red (Eu) and green (Tb) intracellular luminescence under a confocal microscope. Concentration-and time-dependent MTT cell viability assays show that the nanobundles show low toxicity towards cells which makes them promising in bioimaging field.

Stimuli-responsive colorimetric and NIR fluorescence combination probe for selective reporting of cellular hydrogen peroxide

Hydrogen peroxide (H2O2) is a key reactive oxygen species and a messenger in cellular signal transduction apart from playing a vital role in many biological processes in living organisms. In this article, we present phenyl boronic acid-functionalized quinone-cyanine (QCy-BA) in combination with AT-rich DNA (exogenous or endogenous cellular DNA), i.e., QCy-BA subset of DNA as a stimuli-responsive NIR fluorescence probe for measuring in vitro levels of H2O2. In response to cellular H2O2 stimulus, QCy-BA converts into QCy-DT, a one-donor-two-acceptor (D2A) system that exhibits switch-on NIR fluorescence upon binding to the DNA minor groove. Fluorescence studies on the combination probe QCy-BA subset of DNA showed strong NIR fluorescence selectively in the presence of H2O2. Furthermore, glucose oxidase (GOx) assay confirmed the high efficiency of the combination probe QCy-BA subset of DNA for probing H2O2 generated in situ through GOx-mediated glucose oxidation. Quantitative analysis through fluorescence plate reader, flow cytometry and live imaging approaches showed that QCy-BA is a promising probe to detect the normal as well as elevated levels of H2O2 produced by EGF/Nox pathways and post-genotoxic stress in both primary and senescent cells. Overall, QCy-BA, in combination with exogenous or cellular DNA, is a versatile probe to quantify and image H2O2 in normal and disease-associated cells.

Holographic methods for the fabrication of various types of mirrors

A comprehensive set of new configurations for the holographic simulation of a wide variety of mirrors is described. These holographically simulated mirrors (HSMs) have been experimentally realized and their imaging performance has been studied.

Photocatalytic Inactivation of Escherichia coli with LbL Fabricated Immobilized TiO2 Thin Films

Photocatalysis using semiconductor catalyst such as TiO2, in presence of UV light, is a promising technique for the inactivation of various microorganisms present in water. In the current study, the photocatalytic inactivation of Escherichia coli bacteria was studied with commercial Degussa Aeroxide TiO2 P25 (Aeroxide) and combustion synthesized TiO2 (CS TiO2) catalysts immobilized on glass slides in presence of UV irradiation. Thin films of the catalyst and polyelectrolytes, poly(allyl amine hydrochloride) and poly(styrene sulfonate sodium salt), were deposited on glass slides by layer by layer (LbL) deposition method and characterized by SEM and AFM imaging. The effect of various parameters, namely, catalyst concentration, surface area and number of bilayers, on inactivation was studied. Maximum inactivation of 8-log reduction in the viable count was observed with 1.227 mg/cm(2) of catalyst loaded slides. With this loading, complete inactivation was observed within 90 min and 75 min of irradiation, for Aeroxide and CS TiO2, respectively. Further increase in the catalyst concentration or increasing number of bilayers had no significant effect on inactivation. The effect of surface area on the inactivation was studied by increasing the number of slides and the inactivation was observed to increase with increasing surface area. It was also observed that the immobilized catalyst slides can be used for several cycles leading to an economic process. The study shows potential application of TiO2, for the inactivation of bacteria, in its fixed form by a simple immobilization technique.

Highly fluorescent GFPm2+-based genome integration-proficient promoter probe vector to study Mycobacterium tuberculosis promoters in infected macrophages

Study of activity of cloned promoters in slow-growing Mycobacterium tuberculosis during long-term growth conditions in vitro or inside macrophages, requires a genome-integration proficient promoter probe vector, which can be stably maintained even without antibiotics, carrying a substrate-independent, easily scorable and highly sensitive reporter gene. In order to meet this requirement, we constructed pAKMN2, which contains mycobacterial codon-optimized gfpm2+ gene, coding for GFPm2+ of highest fluorescence reported till date, mycobacteriophage L5 attP-int sequence for genome integration, and a multiple cloning site. pAKMN2 showed stable integration and expression of GFPm2+ from M. tuberculosis and M. smegmatis genome. Expression of GFPm2+, driven by the cloned minimal promoters of M. tuberculosis cell division gene, ftsZ (MtftsZ), could be detected in the M. tuberculosis/pAKMN2-promoter integrants, growing at exponential phase in defined medium in vitro and inside macrophages. Stable expression from genome-integrated format even without antibiotic, and high sensitivity of detection by flow cytometry and fluorescence imaging, in spite of single copy integration, make pAKMN2 useful for the study of cloned promoters of any mycobacterial species under long-term in vitro growth or stress conditions, or inside macrophages.

Flexible poly(vinyl alcohol-co-ethylene)/modified MMT moisture barrier composite for encapsulating organic devices

Flexible, nano-composite moisture barrier films of poly(vinyl alcohol-co-ethylene) with surface modified montmorillonite fabricated by solution casting were used to encapsulate organic devices. The composite films were characterized by FTIR, UV-visible spectroscopy and SEM imaging. Thermal and mechanical properties of the composite films were studied by DSC and UTM. Calcium degradation test was used to determine the transmission rate of water vapour through the composite films, which showed a gradual reduction from similar to 0.1 g m(-2) day(-1) to 0.0001 g m(-2) day(-1) with increasing modified montmorillonite loading in the neat copolymer. The increase in moisture barrier performance is attributed to the decreased water vapour diffusivity due to matrix-filler interactions in the composite. The accelerated aging test was carried out for non-encapsulated and encapsulated devices to evaluate the efficiency of the encapsulants. The encapsulated devices exhibited longer lifetimes indicating the efficacy of the encapsulant.

Guided Ultrasonic Wave Propagation through Inaccessible Damage in a Folded Plate using Sensor-Actuator Network

Rapid diagnostics and virtual imaging of damages in complex structures like folded plate can help reduce the inspection time for guided wave based NDE and integrated SHM. Folded plate or box structure is one of the major structural components for increasing the structural strength. Damage in the folded plate, mostly in the form of surface breaking cracks in the inaccessible zone is a usual problem in aerospace structures. One side of the folded plate is attached (either riveted or bonded) to adjacent structure which is not accessible for immediate inspection. The sensor-actuator network in the form of a circular array is placed on the accessible side of the folded plate. In the present work, a circular array is employed for scanning the entire folded plate type structure for damage diagnosis and wave field visualization of entire structural panel. The method employs guided wave with relatively low frequency bandwidth of 100-300 kHz. Change in the response signal with respect to a baseline signal is used to construct a quantitative relationship with damage size parameters. Detecting damage in the folded plate by using this technique has significant potential for off-line and on-line SHM technologies. By employing this technique, surface breaking cracks on inaccessible face of the folded plate are detected without disassembly of structure in a realistic environment.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Multivariate Granger causality: an estimation framework based on factorization of the spectral density matrix

Granger causality is increasingly being applied to multi-electrode neurophysiological and functional imaging data to characterize directional interactions between neurons and brain regions. For a multivariate dataset, one might be interested in different subsets of the recorded neurons or brain regions. According to the current estimation framework, for each subset, one conducts a separate autoregressive model fitting process, introducing the potential for unwanted variability and uncertainty. In this paper, we propose a multivariate framework for estimating Granger causality. It is based on spectral density matrix factorization and offers the advantage that the estimation of such a matrix needs to be done only once for the entire multivariate dataset. For any subset of recorded data, Granger causality can be calculated through factorizing the appropriate submatrix of the overall spectral density matrix.

History of MRI

A brief account of the basic principle and methodologies of MRI technique, right from its beginning, are outlined. The final pulse sequence used for MRI using Fourier Imaging (phase encoding), Echo-Planar Imaging (EPI) for detection of a whole plane in a single excitation and T-1 and T-2 contrast enhancement is explained. The various associated methods such as, MR-spectroscopy, flow measurement (MRI-angiography), Lung-imaging using hyperpolarized Xe-129 and He-3 and functional imaging (f-MRI) are described.

3D Macroporous Solids from Chemically Cross-linked Carbon Nanotubes

We demonstrate a new technique to generate multiple light-sheets for fluorescence microscopy. This is possible by illuminating the cylindrical lens using multiple copies of Gaussian beams. A diffraction grating placed just before the cylindrical lens splits the incident Gaussian beam into multiple beams traveling at different angles. Subsequently, this gives rise to diffraction-limited light-sheets after the Gaussian beams pass through the combined cylindrical lens-objective sub-system. Direct measurement of field at and around the focus of objective lens shows multi-sheet pattern with an average thickness of 7.5 μm and inter-sheet separation of 380 μm. Employing an independent orthogonal detection sub-system, we successfully imaged fluorescently-coated yeast cells (≈4 μm) encaged in agarose gel-matrix. Such a diffraction-limited sheet-pattern equipped with dedicated detection system may find immediate applications in the field of optical microscopy and fluorescence imaging. © 2015 Optical Society of America

Comparative evaluation of inversion approaches of the radiative transfer model for estimation of crop biophysical parameters

The inversion of canopy reflectance models is widely used for the retrieval of vegetation properties from remote sensing. This study evaluates the retrieval of soybean biophysical variables of leaf area index, leaf chlorophyll content, canopy chlorophyll content, and equivalent leaf water thickness from proximal reflectance data integrated broadbands corresponding to moderate resolution imaging spectroradiometer, thematic mapper, and linear imaging self scanning sensors through inversion of the canopy radiative transfer model, PROSAIL. Three different inversion approaches namely the look-up table, genetic algorithm, and artificial neural network were used and performances were evaluated. Application of the genetic algorithm for crop parameter retrieval is a new attempt among the variety of optimization problems in remote sensing which have been successfully demonstrated in the present study. Its performance was as good as that of the look-up table approach and the artificial neural network was a poor performer. The general order of estimation accuracy for para-meters irrespective of inversion approaches was leaf area index > canopy chlorophyll content > leaf chlorophyll content > equivalent leaf water thickness. Performance of inversion was comparable for broadband reflectances of all three sensors in the optical region with insignificant differences in estimation accuracy among them.