Gold Nanorods as a Contrast Agent for Doppler Optical Coherence Tomography

Wang, Bo; Kagemann, Larry; Schuman, Joel S.; Ishikawa, Hiroshi; Bilonick, Richard A.; Ling, Yun; Sigal, Ian A.; Nadler, Zach; Francis, Andrew; Sandrian, Michelle Gabriele; Wollstein, Gadi

doi:10.1371/journal.pone.0090690

Cited by 29 publications

(30 citation statements)

References 18 publications

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“…Our custom synthesized GNRs 15 provide better depth and resolution in OCT compared to smaller GNRs used in previous studies to enhance contrast in tissues and in vivo. 8,12,13 We further demonstrated that leukocytes obtained from mouse blood and spleen tissue can be successfully labeled with scattering contrast agents such as GNRs via a targeted labeling strategy. Such GNR-labeling can be utilized to enhance scattering intensity of these otherwise poorly scattering cells, allowing them to be detected by OCT.…”

Section: Discussionmentioning

confidence: 93%

“…GNRs have been recently used to enhance OCT signals in tissue mimicking phantoms, [7][8][9][10][11] excised porcine eyes, 8 vitreous of mice eyes, 12 anterior chambers and cornea of mice eyes, 13 and in mouse mammary tumors. 14 Additionally, using our custom synthesized GNRs (∼100 × 30 nm), we have achieved ultrahigh detection sensitivity in vivo.…”

Section: Introductionmentioning

confidence: 99%

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High-resolution contrast-enhanced optical coherence tomography in mice retinae

et al. 2016

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Abstract. Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of ∼0.5 nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

High-resolution contrast-enhanced optical coherence tomography in mice retinae

et al. 2016

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“…Focal changes of conventional aqueous humor outflow are difficult to examine, 8,28 yet are crucial to better understand how elements downstream of the TM may influence outflow. There is ample new clinical evidence [29][30][31][32][33] that very significant outflow resistance exists downstream of the trabecular meshwork as trabecular ablation rarely achieves the theoretically lowest intraocular pressure, which would be equal to that of episcleral venous pressure according to the Goldmann equation.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 The trabecular meshwork and the aqueous spaces of Schlemm's canal and collector channels in the superficial to midlevel sclera can also be imaged noninvasively by spectraldomain optical coherence tomography (SD-OCT). 7 Wang et al 8 used a Doppler strategy to detect movements of gold nanorods by SD-OCT but a quantification of flow could not be obtained. This approach may have limited use in vivo due to toxicity.…”

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confidence: 99%

Quantification of Focal Outflow Enhancement using Differential Canalograms

Loewen

Brown

Scott

et al. 2016

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PURPOSE. To quantify regional changes of conventional outflow caused by ab interno trabeculectomy (AIT).METHODS. Gonioscopic, plasma-mediated AIT was established in enucleated pig eyes. We developed a program to automatically quantify outflow changes (R, package eye-canalogram, github.com) using a fluorescent tracer reperfusion technique. Trabecular meshwork (TM) ablation was demonstrated with fluorescent spheres in six eyes before formal outflow quantification with two-dye reperfusion canalograms in six additional eyes. Eyes were perfused with a central, intracameral needle at 15 mm Hg. Canalograms and histology were correlated for each eye. RESULTS.The pig eye provided a model with high similarity to AIT in human patients. Histology indicated ablation of TM and unroofing of most Schlemm's canal segments. Spheres highlighted additional circumferential and radial outflow beyond the immediate area of ablation. Differential canalograms showed that AIT caused an increase of outflow of 17 6 5-fold inferonasally, 14 6 3-fold superonasally, and also an increase in the opposite quadrants with a 2 6 1-fold increase superotemporally, and 3 6 3 inferotemporally. Perilimbal specific flow image analysis showed an accelerated nasal filling with an additional perilimbal flow direction into adjacent quadrants. CONCLUSIONS.A quantitative, differential canalography technique was developed that allows us to quantify supraphysiological outflow enhancement by AIT.

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“…The advantages of LSPR make Cu-Sn-S nanocrystals can serve as a contrast-enhanced molecular imaging for cancer detection in clinical setting. Such as Optical Coherence Tomography (OCT), [28][29][30][31][32] magnetic resonance imaging (MRI) and positron emission tomography (PET). As we know, there are many researches have reported the synthesis and characterization of Cu-Sn-S nanocrystals.…”

Section: Introductionmentioning

confidence: 99%

Characterizing physical properties and in vivo OCT imaging study of Cu-Sn-S nanocrystals

et al. 2017

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Highly yield Cu2SnS3 nanocrystals (CTS NCs) have been attracted more attentions in these years, the CTS NCs with strong absorption in near-infrared (NIR) region which can serve as the contrast agent of Optical Coherence Tomography (OCT) imaging. These NCs can be synthesized by facile method, and exhibit a Localized Surface Plasmon Resonance (LSPR) peak in NIR region. The LSPR peak position of the CTS NCs depends on the ratio of copper to tin in the synthesis process. The highest intensity of LSPR at 1380nm when Cu:Sn ratio reach to 9:1. The TEM analysis and X-ray diffraction pattern reveals the formation of CTS NCs with an average size of 6nm and the structure is kesterite crystal phase. In order to apply the NCs in vivo and in vitro study, we used PEGylated phospholipid (DSPE-PEG) to modified NCs, and the colloidal stability and cell viability of DSPE-PEG CTS NCs are very suitable for the in vivo OCT imaging study. To quantitatively analyze the contrast effect of DSPE-PEG CTS NCs, the contrast agent was injected from the tail vein of ICR mice, then applied the SD-OCT system monitor the vein of the mouse pinna for 30 minutes. The results indicated that the DSPE-PEG CTS NCs created an obvious signal in the OCT imaging process, which provide the basis for the application of CTS NCs as the contrast agent for the bioimaging study.

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Gold Nanorods as a Contrast Agent for Doppler Optical Coherence Tomography

Cited by 29 publications

References 18 publications

High-resolution contrast-enhanced optical coherence tomography in mice retinae

High-resolution contrast-enhanced optical coherence tomography in mice retinae

Quantification of Focal Outflow Enhancement using Differential Canalograms

Characterizing physical properties and in vivo OCT imaging study of Cu-Sn-S nanocrystals

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