Optical imaging with dynamic contrast agents

Biological imaging applications often employ molecular probes or nanoparticles for enhanced contrast. However, resolution and detection are still often limited by the intrinsic heterogeneity of the sample, which can produce high levels of background that obscure the signals of interest. Herein, we describe approaches to overcome this obstacle based on the concept of dynamic contrast: a strategy for elucidating signals by the suppression or removal of background noise. Dynamic contrast mechanisms can greatly reduce the loading requirement of contrast agents, and may be especially useful for single-probe imaging. Dynamic contrast modalities are also platform-independent, and can enhance the performance of sophisticated biomedical imaging systems or simple optical microscopes alike. Dynamic contrast is performed in two stages: 1) a signal modulation scheme to introduce time-dependent changes in amplitude or phase, and 2) a demodulation step for signal recovery. Optical signals can be coupled with magnetic nanoparticles, photoswitchable probes, or plasmon-resonant nanostructures for modulation by magnetomotive, photonic, or photothermal mechanisms, respectively. With respect to image demodulation, many of the strategies developed for signal processing in electronics and communication technologies can also be applied toward the editing of digital images. The image-processing step can be as simple as differential imaging, or may involve multiple reference points for deconvolution by using cross-correlation algorithms. Periodic signals are particularly amenable to image demodulation strategies based on Fourier transform; the contrast of the demodulated signal increases with acquisition time, and modulation frequencies in the kHz range are possible. Dynamic contrast is an emerging topic with considerable room for development, both with respect to molecular or nanoscale probes for signal modulation, and also to methods for more efficient image processing and editing.     

Alignment of low‐dose X‐ray fluorescence tomography images using differential phase contrast

X‐ray fluorescence nanotomography provides unprecedented sensitivity for studies of trace metal distributions in whole biological cells. Dose fractionation, in which one acquires very low dose individual projections and then obtains high statistics reconstructions as signal from a voxel is brought together (Hegerl & Hoppe, 1976), requires accurate alignment of these individual projections so as to correct for rotation stage runout. It is shown here that differential phase contrast at 10.2 keV beam energy offers the potential for accurate cross‐correlation alignment of successive projections, by demonstrating that successive low dose, 3 ms per pixel, images acquired at the same specimen position and rotation angle have a narrower and smoother cross‐correlation function (1.5 pixels FWHM at 300 nm pixel size) than that obtained from zinc fluorescence images (25 pixels FWHM). The differential phase contrast alignment resolution is thus well below the 700 nm × 500 nm beam spot size used in this demonstration, so that dose fractionation should be possible for reduced‐dose, more rapidly acquired, fluorescence nanotomography experiments.     

X射线衍射增强相衬成像的实验结果

报道了X射线衍射增强相衬成像的最新实验结果,简要论述了其原理,证明了衍射增强X射线相衬成像是一种高信噪比的成像方法,它比普通的X射线成像和层析(CT)具有高得多的分辨力,约为10μm,这在临床医学、材料科学及其它一些生物研究领域具有巨大的应用潜力。     

聚酯型核磁共振造影剂的合成及体外弛豫性能研究

本文通过三种甘醇，己二醇和对苯二酚与ＤＴＰＡ双酸酐共聚，合成了五个大分子配体，这些配体与Ｇｄ２Ｏ３反应制得相应的配合物，配体和配合物都有较好的水溶性。由三种甘醇制得的配体形成的配合物具有比Ｇｄ（ＤＴＰＡ）更好的弛豫性能。     

Orientational control of liquid crystal molecules via carbon nanotubes and dichroic dye in polymer dispersed liquid crystal

Polymer dispersed liquid crystals (PDLCs) using nematic liquid crystal and photo-curable polymer (NOA 65) were prepared by polymerisation-induced phase separation technique, in equal ratio (1:1) of polymer and liquid crystal (LC). We demonstrate that doping of small amount (0.125%, wt./wt.) of multiwall carbon nanotubes (CNTs) and orange azo dichroic dye in PDLC generously controlled the molecular orientation, dynamics of LC in droplet and size of droplets. The effects of multiwall CNTs and dye on PDLCs were studied in terms of transition temperature, droplet morphology, transmittance characteristic, contrast ratio and response time. The results exhibited that the values of the threshold electric fields were reduced from 8 V/µm (pure PDLC) to 1.18 and 1.72 V/µm, doped with multiwall CNTs and dye, respectively. The CNTs-doped PDLC shows faster switching response as compared with pure PDLC and dye-doped PDLC. However, dye-doped PDLC shows much higher contrast among all PDLC samples. Further, the results also illustrate that the birefringence value of LC in PDLCs was changed with doping of CNTs and dye.     

First experiments on the Australian Synchrotron Imaging and Medical beamline,including investigations of the effective source size in respect of X‐ray imaging

The Imaging and Medical beamline at the Australian Synchrotron achieved `first light' in December 2008. Here, the first experiments performed on the beamline are reported, which involved both X‐ray imaging and tomography studies for a range of samples. The use of a plastic‐edge phantom for quantitative measurements of contrast and resolution proved to be very instructive and helped to confirm certain parameter values such as the effective horizontal source size, detector resolution and average X‐ray energy for the polychromatic beam.     

Optical microscopic, synchrotron X-ray topographic and reticulographic study of homoepitaxial CVD diamond

Surface topography and crystal-lattice perfection of homoepitaxial layers deposited by microwave plasma CVD on (0 0 1) and near-(0 0 1) facets polished on HPHT synthetic diamond are described. Optical micrographic techniques included birefringence, Nomarski and 2-beam interference. The synchrotron X-ray experiments comprised Laue topography plus a recently developed sensitive misorientation-measuring technique, reticulography. Two special circumstances enhanced information yield from the experiments. First, the substrate crystal was unusually strain-free and had a very low dislocation content. Second, epilayer growth had taken place in two stages, depositing thicknesses of 10 μm and 30–34 μm, respectively. This double deposition complicated the observations, but added features of scientific and practical interest. Epilayer cracking finally present had occurred almost entirely before the second growth stage. With assistance from quantitative data provided by reticulography, the X-ray diffraction properties of the substrate and epilayers are analysed. Lattice misorientations on the untreated lower surface of the substrate were only 1 arcsec except close to growth-sector boundaries and dislocation outcrops. The final epilayer growth surface above areas where cracking in the first epilayer was absent or sparse exhibited near-perfect-crystal diffraction behaviour.     

Tantalum Oxide Nanoparticles for the Imaging of Articular Cartilage Using X‐Ray Computed Tomography: Visualization of Ex Vivo/In Vivo Murine Tibia and Ex Vivo Human Index Finger Cartilage

The synthesis and characterization of tantalum oxide (Ta₂O₅) nanoparticles (NPs) as new X‐ray contrast media for microcomputed tomography (μCT) imaging of articular cartilage are reported. NPs, approximately 5–10 nm in size, and possessing distinct surface charges, were synthesized using phosphonate (neutral), ammonium (cationic), and carboxylate (anionic) ligands as end functional groups. Assessment of a cartilage defect in a human cadaver distal metacarpophalangeal (MCP) joint with the ammonium nanoparticles showed good visualization of damage and preferential uptake in areas surrounding the defect. Finally, an optimized nontoxic cationic NP contrast agent was evaluated in an in vivo murine model and the cartilage was imaged. These nanoparticles represent a new type of contrast agent for imaging articular cartilage, and the results demonstrate the importance of surface charge in the design of nanoparticulate agents for targeting the surface or interior zones of articular cartilage.     

Novel macrocyclic EuII complexes: fast water exchange related to an extreme M-O water distance

Eu(II) complexes are potential candidates for pO(2)-responsive contrast agents in magnetic resonance imaging. In this regard, we have characterized two novel macrocyclic Eu(II) chelates, [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) (H(4)DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, H(4)TETA=1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) in terms of redox and thermodynamic complex stability, proton relaxivity, water exchange, rotation and electron spin relaxation. Additionally, solid-state structures were determined for the Sr(II) analogues. They revealed no inner-sphere water in the TETA and one inner-sphere water molecule in the DOTA complex. This hydration pattern is retained in solution, as the (17)O chemical shifts and (1)H relaxation rates proved for the corresponding Eu(II) compounds. The thermodynamic complex stability, determined from the formal redox potential and by pH potentiometry, of [Eu(II)(DOTA)(H(2)O)](2-) (lg K(Eu(II))=16.75) is the highest among all known Eu(II) complexes, whereas the redox stabilities of both [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) are inferior to that of 18-membered macrocyclic Eu(II) chelates. Variable-temperature (17)O NMR, NMRD and EPR studies yielded the rates of water exchange, rotation and electron spin relaxation. Water exchange on [Eu(II)(DOTA)(H(2)O)](2-) is remarkably fast (k298(ex)=2.5 x 10(9) s(-1)). The near zero activation volume (DeltaV++ =+0.1+/-1.0 cm(3) mol(-1)), determined by variable-pressure (17)O NMR spectroscopy, points to an interchange mechanism. The fast water exchange can be related to the low charge density on Eu(II), to an unexpectedly long M-O(water) distance (2.85 A) and to the consequent interchange mechanism. Electron spin relaxation is considerably slower on [Eu(II)(DOTA)(H(2)O)](2-) than on the linear [Eu(II)(DTPA)(H(2)O)](3-) (H(5)DTPA=diethylenetriaminepentaacetic acid), and this difference is responsible for its 25 percent higher proton relaxivity (r(1)=4.32 mM(-1) s(-1) for [Eu(II)(DOTA)(H(2)O)](2-) versus 3.49 mM(-1) s(-1) for [Eu(II)(DTPA)(H(2)O)](3-); 20 MHz, 298 K).     

Determination of residual solvents and reagents in X-ray contrast media by automatic static headspace capillary gas chromatography

A specific, sensitive, and simple method for the quantitation of residual methanol, 2-propanol, 2-butanol, 2-methoxy-1-ethanol, 1-chloro-3-methoxy-2-propanol, 3-chloro-2-methoxy-1-propanol, and 1,3-dimethoxy-2-propanol in two non-ionic X-ray contrast media, has been developed. The headspace of a 25 % w/V aqueous solution of contrast media, obtained at 90–110°C in 15 min, was injected onto a capillary column coated with cyanopropyl, phenyl, dimethylpolysiloxane polymer. The internal standards used were 2-pentanol and 3-methoxy-1-butanol. The limits of detection were below 5 μg/g. The repeatability of the method at 50 μg/g of each solvent was below 5 %; and at 100 μg/g of the methoxypropanol compounds and 2-methoxy-1-ethanol, below 10 % (RSD, N = 5).