June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Multimodal Photoacoustic Microscopy and OCT Molecular Imaging of Choroidal Neovascularization using Chain-like Gold Nanoparticles
Author Affiliations & Notes
  • Yannis Mantas Paulus
    Ophthalmology, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Van Phuc Nguyen
    Ophthalmology, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Wei Qian
    IMRA Inc, Michigan, United States
  • Yanxiu Li
    Ophthalmology, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Bing Liu
    IMRA Inc, Michigan, United States
  • Michael Aaberg
    Ophthalmology, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Jessica Henry
    Ophthalmology, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Wei Zhang
    Ophthalmology, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Xueding Wang
    Ophthalmology, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Yannis Paulus, None; Van Phuc Nguyen, None; Wei Qian, IMRA Inc (E); Yanxiu Li, None; Bing Liu, IMRA Inc (E); Michael Aaberg, None; Jessica Henry, None; Wei Zhang, None; Xueding Wang, None
  • Footnotes
    Support  NEI 1K08EY027458 ; Fight for Sight – International Retinal Research Foundation FFSGIA16002 ; Research to Prevent Blindness ; University of Michigan
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3496. doi:
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    • Get Citation

      Yannis Mantas Paulus, Van Phuc Nguyen, Wei Qian, Yanxiu Li, Bing Liu, Michael Aaberg, Jessica Henry, Wei Zhang, Xueding Wang; Multimodal Photoacoustic Microscopy and OCT Molecular Imaging of Choroidal Neovascularization using Chain-like Gold Nanoparticles. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3496.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Functional and molecular retinal imaging can enable earlier diagnosis and improved monitoring. Gold nanoparticles serve as promising contrast agents, yet their utility is limited due to their absorption spectrum overlapping with that of hemoglobin. This report describes a novel ultrapure chain-like gold nanoparticle (CGNP) that exhibits a redshifted peak wavelength at 650 nm to perform molecular imaging of choroidal neovascularization (CNV).

Methods : CGNP are fabricated using femtosecond laser and conjugated to RGD (CGNP-RGD). The optical and physical characteristics of the CGNP-RGD are evaluated. A multimodal photoacoustic microscopy (PAM) and Ganymede-II-HR OCT retinal imaging system has been developed. Rabbits (N=6) were treated with subretinal injection of Matrigel and human VEGF-165 to induce CNV and imaged before and at 2 h, 24 h, 48 h, 72 h, 4, 5, 7, 9, 11 and 14 days after intravenous administration of CGNP-RGD 0.4 mL at 2.5 mg/mL.

Results : The synthesized CGNP show excellent biocompatibility and photostability. PAM at 578 nm visualized the vasculature whereas PAM at 650 nm imaged the CGNP selectively. RGD functionalization allowed targeting of CNV. Intravenous injection of CGNP-RGD provided up to a 15-fold increase in PAM signal at 650 nm (from 0.13 ± 0.001 to 1.97 ± 0.02 (a.u.) for pre- and 2h post-injection; p < 0.001). The PAM signal reached to the maximum at 48 h before decreasing from day 7 to 14. PAM signal did not vary more than 2% between 3 sequential scans, indicating CGNP stability. CGNP caused a 176% increase in OCT signal. Histology indicates that CGNP clusters can disassemble, which may facilitate its clearance.

Conclusions : This study describes a novel multimodal PAM and OCT contrast agent CGNP. These CGNP-RGD led to a 15-fold increase in PAM amplitude and 176% increase in OCT signal for molecular imaging of CNV.

This is a 2020 ARVO Annual Meeting abstract.

 

Multimodal molecular imaging of CNV: (a) Fundus photography. (b-d) ICG angiography early, middle, and late phase images demonstrating CNV (white arrows). (e & f) OCT acquired along the selected line in Fig A before and 2 h after CGNPs. PAM images at excitation wavelengths of 578 nm and 650 nm before (g & h) and after (j & k) CGNP-RGD demonstrating selective visualization of CNV only at 650 nm provided by CGNP-RGD. (i & l) 3D PAM before and after CGNP-RGD administration distinguishing CNV (pseudo green color) from normal vessels.

Multimodal molecular imaging of CNV: (a) Fundus photography. (b-d) ICG angiography early, middle, and late phase images demonstrating CNV (white arrows). (e & f) OCT acquired along the selected line in Fig A before and 2 h after CGNPs. PAM images at excitation wavelengths of 578 nm and 650 nm before (g & h) and after (j & k) CGNP-RGD demonstrating selective visualization of CNV only at 650 nm provided by CGNP-RGD. (i & l) 3D PAM before and after CGNP-RGD administration distinguishing CNV (pseudo green color) from normal vessels.

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