A Multimode Optical Imaging System for Preclinical Applications In Vivo: Technology Development, Multiscale Imaging, and Chemotherapy Assessment

Hwang, Jae Youn; Wachsmann‐Hogiu, Sebastian; Ramanujan, V. Krishnan; Ljubimova, Julia Y.; Gross, Zeev; Gray, Harry B.; Medina-Kauwe, Lali K.; Farkas, Daniel L.

doi:10.1007/s11307-011-0517-z

Cited by 23 publications

(31 citation statements)

References 41 publications

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“…Bio-optical imaging is increasingly used to monitor bacterial presence longitudinally in live animals (Daghighi et al, 2012). Bio-optical imaging can either be performed in a bioluminescence or fluorescence mode (Hwang et al, 2012;Ponomarev et al, 2004). A number of bioluminescent bacterial strains are available for longitudinal monitoring of bacterial persistence.…”

Section: Mmp-and Integrin-expression In Baimentioning

confidence: 99%

Real-time quantification of matrix metalloproteinase and integrin αvβ3 expression during biomaterial-associated infection in a murine model

Daghighi

Sjollema²,

Dijkstra³

et al. 2014

eCM

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Biomaterial implants and devices increase the risk of microbial infections due to the biofilm mode of growth of infecting bacteria on implant materials, in which bacteria are protected against antibiotic treatment and the local immune system. Matrix-metalloproteinases (MMPs) and cell surface integrin receptors facilitate transmigration of inflammatory cells toward infected or inflamed tissue. This study investigates the relationship between MMP-and integrin-expression and the clearance of infecting Staphylococcus aureus around implanted biomaterials in a murine model. MMP-and integrin αvβ3-expression were monitored in mice, with and without subcutaneously implanted biomaterial samples, in the absence and presence of bioluminescent S. aureus Xen36. Staphylococcal persistence was imaged longitudinally over time using bioluminescence imaging. The activatable MMPSense ® 680 and integrin-targeted IntegriSense ® 750 probes were injected on different days after implantation and their signal intensity and localisation monitored using fluorescence imaging. After sacrifice 7 or 16 days postimplantation, staphylococci from biomaterial samples and surrounding tissues were cultured on agar-plates and presence of host inflammatory cells was histologically evaluated. MMP-and integrin-expression were equally enhanced in presence of staphylococci or biomaterials up to 7 days post-implantation, but their localisation along the biomaterial samples differed. Bacterial clearance from tissue was higher in the absence of biomaterials. It is of clinical relevance that MMP-and integrin-expression were enhanced in presence of both staphylococci and biomaterials, although the immune system in the presence of biomaterials remained hampered in eradicating bacteria during the first 7 days post-implantation.

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Section: Mmp-and Integrin-expression In Baimentioning

confidence: 99%

Real-time quantification of matrix metalloproteinase and integrin αvβ3 expression during biomaterial-associated infection in a murine model

Daghighi

Sjollema²,

Dijkstra³

et al. 2014

eCM

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“…The procedures below entail the use of a customized macro-illumination and detection system (Figure 1) 8 .…”

Section: Protocolmentioning

confidence: 99%

Analysis of Targeted Viral Protein Nanoparticles Delivered to HER2+ Tumors

Hwang

Farkas

Medina-Kauwe

2013

JoVE

Self Cite

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The HER2+ tumor-targeted nanoparticle, HerDox, exhibits tumor-preferential accumulation and tumor-growth ablation in an animal model of HER2+ cancer. HerDox is formed by non-covalent self-assembly of a tumor targeted cell penetration protein with the chemotherapy agent, doxorubicin, via a small nucleic acid linker. A combination of electrophilic, intercalation, and oligomerization interactions facilitate self-assembly into round 10–20 nm particles. HerDox exhibits stability in blood as well as in extended storage at different temperatures. Systemic delivery of HerDox in tumor-bearing mice results in tumor-cell death with no detectable adverse effects to non-tumor tissue, including the heart and liver (which undergo marked damage by untargeted doxorubicin). HER2 elevation facilitates targeting to cells expressing the human epidermal growth factor receptor, hence tumors displaying elevated HER2 levels exhibit greater accumulation of HerDox compared to cells expressing lower levels, both in vitro and in vivo. Fluorescence intensity imaging combined with in situ confocal and spectral analysis has allowed us to verify in vivo tumor targeting and tumor cell penetration of HerDox after systemic delivery. Here we detail our methods for assessing tumor targeting via multimode imaging after systemic delivery.

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“…These probes are based on conjugating targeting ligands with organic molecules or inorganic materials which emit visible or infrared light. Small animal optical imaging platforms contain cameras based on high-sensitivity silicon CCD arrays, with peak quantum efficiency in the visible wavelength region 4,5 . These systems are suitable for assessment of visible-emitting contrast agents, as well as near-infrared agents emitting in the 700-900 nm range.…”

Section: Introductionmentioning

confidence: 99%

Small animal imaging platform for quantitative assessment of short-wave infrared-emitting contrast agents

Mingozzi

Higgins

et al. 2015

SPIE Proceedings

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We report the design, calibration, and testing of a pre-clinical small animal imaging platform for use with short-wave infrared (SWIR) emitting contrast agents. Unlike materials emitting at visible or near-infrared wavelengths, SWIRemitting agents require detection systems with sensitivity in the 1-2 μm wavelength region, beyond the range of commercially available small animal imagers. We used a collimated 980 nm laser beam to excite rare-earth-doped NaYF 4 :Er,Yb nanocomposites, as an example of a SWIR emitting material under development for biomedical imaging applications. This beam was raster scanned across the animal, with fluorescence in the 1550 nm wavelength region detected by an InGaAs area camera. Background adjustment and intensity non-uniformity corrections were applied in software. The final SWIR fluorescence image was overlaid onto a standard white-light image for registration of contrast agent uptake with respect to anatomical features.

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A Multimode Optical Imaging System for Preclinical Applications In Vivo: Technology Development, Multiscale Imaging, and Chemotherapy Assessment

Cited by 23 publications

References 41 publications

Real-time quantification of matrix metalloproteinase and integrin αvβ3 expression during biomaterial-associated infection in a murine model

Real-time quantification of matrix metalloproteinase and integrin αvβ3 expression during biomaterial-associated infection in a murine model

Analysis of Targeted Viral Protein Nanoparticles Delivered to HER2+ Tumors

Small animal imaging platform for quantitative assessment of short-wave infrared-emitting contrast agents

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