Breast imaging technology: Probing physiology and molecular function using optical imaging - applications to breast cancer

The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring

Nanoscale control of Ag nanostructures for plasmonic fluorescence enhancement of near-infrared dyes

Potential utilization of proteins for early detection and diagnosis of various diseases has drawn considerable interest in the development of protein-based detection techniques. Metal induced fluorescence enhancement offers the possibility of increasing the sensitivity of protein detection in clinical applications. We report the use of tunable plasmonic silver nanostructures for the fluorescence enhancement of a near-infrared (NIR) dye (Alexa Fluor 790). Extensive fluorescence enhancement of ∼2 orders of magnitude is obtained by the nanoscale control of the Ag nanostructure dimensions and interparticle distance. These Ag nanostructures also enhanced fluorescence from a dye with very high quantum yield (7.8 fold for Alexa Fluor 488, quantum efficiency (Qy) = 0.92). A combination of greatly enhanced excitation and an increased radiative decay rate, leading to an associated enhancement of the quantum efficiency leads to the large enhancement. These results show the potential of Ag nanostructures as metal induced fluorescence enhancement (MIFE) substrates for dyes in the NIR “biological window” as well as the visible region. Ag nanostructured arrays fabricated by colloidal lithography thus show great potential for NIR dye-based biosensing applications

Microbial and Chemical Characterization of Underwater Fresh Water Springs in the Dead Sea

Due to its extreme salinity and high Mg concentration the Dead Sea is characterized by a very low density of cells most of which are Archaea. We discovered several underwater fresh to brackish water springs in the Dead Sea harboring dense microbial communities. We provide the first characterization of these communities, discuss their possible origin, hydrochemical environment, energetic resources and the putative biogeochemical pathways they are mediating. Pyrosequencing of the 16S rRNA gene and community fingerprinting methods showed that the spring community originates from the Dead Sea sediments and not from the aquifer. Furthermore, it suggested that there is a dense Archaeal community in the shoreline pore water of the lake. Sequences of bacterial sulfate reducers, nitrifiers iron oxidizers and iron reducers were identified as well. Analysis of white and green biofilms suggested that sulfide oxidation through chemolitotrophy and phototrophy is highly significant. Hyperspectral analysis showed a tight association between abundant green sulfur bacteria and cyanobacteria in the green biofilms. Together, our findings show that the Dead Sea floor harbors diverse microbial communities, part of which is not known from other hypersaline environments. Analysis of the water’s chemistry shows evidence of microbial activity along the path and suggests that the springs supply nitrogen, phosphorus and organic matter to the microbial communities in the Dead Sea. The underwater springs are a newly recognized water source for the Dead Sea. Their input of microorganisms and nutrients needs to be considered in the assessment of possible impact of dilution events of the lake surface waters, such as those that will occur in the future due to the intended establishment of the Red Sea−Dead Sea water conduit

Vector Surveillance and Pathogen Detection in the Working Areas of Military Working Dogs in Eastern Austria

Vector-borne diseases play a major role in human and veterinary medicine worldwide. A previous study detected asymptomatic vector-borne pathogens in military working dogs stationed at a military base in eastern Austria, and a follow-up survey of potential arthropod vectors was conducted in spring 2019 and 2020 in the vicinity of the base to evaluate the presence of vectors and their carrier status for a range of canine and zoonotic pathogens. A total of 1324 ticks (nymphs and adults of Ixodes ricinus, comprising 92.9% of the collected specimens, and adults of Haemaphysalis inermis, a tick previously only rarely described in Austria, Haemaphysalis concinna, and Dermacentor reticulatus) were collected by flagging. In 44.1% (125/284) of all pools (n = 284), one infectious agent was found; in 27.8% (79/284) and in 1.1% (3/284), two and three different agents, respectively, could be identified. Overall, 72.9% of the pools contained at least one pathogen (Borrelia spp., Rickettsia spp., Bartonella spp., and Babesia microti). Borrelia mijamotoi, B. lustinaniae, and B. microti were previously only described in single cases in Austria. Mosquitoes were collected with BG-Sentinel traps monthly during the summer of 2019. A total of 71 individuals from 11 species were collected. No filarioid DNA was detected in the mosquito sample pools, although Dirofilaria repens had been present in the dogs from the military site. In conclusion, vector surveillance should be combined with the surveillance of an exposed population whenever possible to estimate the infection risks for dogs and their handlers

Multispectral optoacoustic tomography of myocardial infarction.

Objectives To investigate the feasibility of a high resolution optical imaging strategy for myocardial infarction. Background Near-infrared approaches to imaging cardiovascular disease enable visualization of disease-associated biological processes in vivo. However, even at the scale of small animals, the strong scattering of light prevents high resolution imaging after the first 1–2 mm of tissue, leading to degraded signal localization. Methods Multispectral optoacoustic tomography (MSOT) was used to non-invasively image myocardial infarction (MI) in a murine model of coronary artery ligation at resolutions not possible with current deep-tissue optical imaging methods. Post-MI imaging was based on resolving the spectral absorption signature of a dendritic polyglycerol sulfate-based (dPGS) near-infrared imaging agent targeted to P- and L-selectin. Results In vivo imaging succeeded in detection of the agent in the injured myocardium after intravenous injection. The high anatomic resolution (<200 μm) achieved by the described method allowed signals originating in the infarcted heart to be distinguished from uptake in adjacent regions. Histological analysis found dPGS signal in infarcted areas, originating from leukocytes and endothelial cells. Conclusions MSOT imaging of myocardial infarction provides non-invasive visualization of optical contrast with a high spatial resolution that is not degraded by the scattering of light

Optoacoustic imaging and staging of arthritic inflammation.

Objectives Rheumatoid Arthritis (RA) is one of the most frequent inflammatory diseases, causing pain and disability in the affected joints. Early diagnosis is essential for the efficiency of symptomatic treatment, and relies on careful clinical, serologic and imaging examinations, such as Magnetic Resonance Imaging (MRI), which is both expensive and time consuming. In an effort to provide the biomedical community with a more accessible way to assess arthritis advancement, we investigated the use of multispectral optoacoustic tomography (MSOT) in a murine model to visualize the extent of the inflammation in vivo through a L- and P-selectin targeting contrast agent. Methods Collagen induced arthritis mice were used as a rheumatoid arthritis model of the limb. MSOT was performed using a L- and P-selectin targeting contrast agent (dPGS-NIR provided by Mivenion, Germany) to increase contrast of the arthritic joint, and signal intensity ratios between healthy and arthritic legs were calculated. Contrast enhanced MR imaging as well as clinical observation, lymphocyte/granulocyte ratio and histology served as references. Results MSOT using an inflammation targeting contrast agent allowed for accurate diagnosis of inflammation in the mouse joints and for significant differentiation of inflamed to healthy joints (P = 0.023). The arthritis findings on the MSOT images were confirmed by clinical observation, blood analysis, contrast enhanced MRI and ex vivo histological examinations. Conclusion This study demonstrates that the combination of inflammation targeting contrast agent and optoacoustic tomographic imaging present a promising mean for diagnosis and staging of arthritic inflammation

Donor-two-acceptor dye design:a distinct gateway to NIR fluorescence

\u3cp\u3eThe detection of chemical or biological analytes upon molecular reactions relies increasingly on fluorescence methods, and there is a demand for more sensitive, more specific, and more versatile fluorescent molecules. We have designed long wavelength fluorogenic probes with a turn-ON mechanism based on a donor-two-acceptor π-electron system that can undergo an internal charge transfer to form new fluorochromes with longer π-electron systems. Several latent donors and multiple acceptor molecules were incorporated into the probe modular structure to generate versatile dye compounds. This new library of dyes had fluorescence emission in the near-infrared (NIR) region. Computational studies reproduced the observed experimental trends well and suggest factors responsible for high fluorescence of the donor-two-acceptor active form and the low fluorescence observed from the latent form. Confocal images of HeLa cells indicate a lysosomal penetration pathway of a selected dye. The ability of these dyes to emit NIR fluorescence through a turn-ON activation mechanism makes them promising candidate probes for in vivo imaging applications.\u3c/p\u3