The aggregation of amyloid-β (Aβ) peptides has been associated with the onset of Alzheimer's disease. Here, we report the use of a luminescent dipyridophenazine ruthenium(II) complex to monitor Aβ fibrillization. This complex is not photoluminescent in aqueous solution nor in the presence of monomeric Aβ, but it presents a strong photoluminescence in the presence of Aβ fibril aggregates. One of the advantages of this metal complex is its large Stokes shift (180 nm). Furthermore, the long-lived photoluminescence lifetime of this ruthenium complex allows its use for the detection of fibrillar proteins in the presence of short-lived fluorescent backgrounds, using time-gating technology. We will present evidence of the advantages of dipyridophenazine ruthenium(II) complexes for monitoring protein fibrillization in highly fluorescent media.
Optical imaging offers exquisite sensitivity and resolution for assessing biological tissue in microscopy applications; however, for samples that are greater than a few hundred microns in thickness (such as whole tissue biopsies), spatial resolution is substantially limited by the effects of light scattering. To improve resolution, time-and angular-domain methods have been developed to reject detection of highly scattered light. This work utilizes a modified version of a commonly used Monte Carlo light propagation software package (MCML) to present the first comparison of time-and angular-domain improvements in spatial resolution with respect to varying sample thickness and optical properties (absorption and scattering). Specific comparisons were made at various tissue thicknesses (1-6 mm) assuming either typical (average) soft tissue scattering properties, μ s ' = 10 cm −1 , or low scattering properties, μ s ' = 3.4 cm −1 , as measured in lymph nodes.
Identification of cancer spread to tumor-draining lymph nodes offers critical information for guiding treatment in many cancer types. Current clinical methods of nodal staging are invasive and can have substantial negative side effects. Molecular imaging protocols have long been proposed as a less invasive means of nodal staging, having the potential to enable highly sensitive and specific evaluations. This review article summarizes the current status and future perspectives for molecular targeted nodal staging.
This work concerns a fluorescence optical projection tomography system for low scattering tissue, like lymph nodes, with angular-domain rejection of highly scattered photons. In this regime, filtered backprojection (FBP) image reconstruction has been shown to provide reasonable quality images, yet here a comparison of image quality between images obtained by FBP and iterative image reconstruction with a Monte Carlo generated system matrix, demonstrate measurable improvements with the iterative method. Through simulated and experimental phantoms, iterative algorithms consistently outperformed FBP in terms of contrast and spatial resolution. Moreover, when projection number was reduced, in order to reduce total imaging time, iterative reconstruction suppressed artifacts that hampered the performance of FBP reconstruction (structural similarity of the reconstructed images with “truth” was improved from 0.15 ± 1.2 × 10−3 to 0.66 ± 0.02); and although the system matrix was generated for homogenous optical properties, when heterogeneity (62.98 cm-1 variance in µs) was introduced to simulated phantoms, the results were still comparable (structural similarity homo: 0.67 ± 0.02 vs hetero: 0.66 ± 0.02).
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