1. Dr. Rinat Ankri and Dr. Dror Fixler
Gold Nanorods as Absorption Contrast Agents for Noninvasive Detection of Cancer and Arterial Vascular Disorders
Dr. Rinat Ankri and Dr. Dror Fixler
Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Israel

2. Light Interaction with a Turbid Medium
Input
Specular
Reflection
Diffuse
Reflection
Scattering
Absorption
Direct Transmission
Diffuse Transmission

3. Light Path in Irradiated Tissues- The Diffusion Theory
Where:
m= ?
Thus, the diffusion reflection (DR) intensity depends on µa and µs’:
Where: ρ= light source-detector distance
m = 1 or 2
Schmitt et al., 1990

4. The experimental set-up
250 µm per step
650 nm
PD Output
Digital Scope
PD Input
Optical fiber PD
The experimental set-up
Sample
Fiber Optic
Detector
1mm
250 µm per step

5. The Diffusion Theory; m=1
Simulation
Expected µs’=1.6 mm-1*
Experiments
Experimental µs’~2.8 mm-1
* Cubeddu et.al., 1993

6. The Diffusion Theory; m=2
Expected µs’=1.6 mm-1*
* Cubeddu et.al., 1993
m= 2 !
Simulation
Experimental µs’~1.5 mm-1
Experiments
Ankri et.al, The Open Optics Journal, 2011

7. Diffusion Reflection and Gold Nano Particles

8. Structural Imaging Molecular Imaging

9. “Fantastic Voyage” Isaac Asimov (1966)
The Vision

10. Why Gold?

11. TEM
FAAS CT
Subcellular
Cellular
Whole body

12. Hand with Ring (Wilhelm Röntgen,1895)
The Concept
Hand with Ring (Wilhelm Röntgen,1895)

13. GNP’s as blood contrast agents

14. Surface plasmon resonance
When a nanoparticle is much smaller than the wave length of light, coherent oscillation of the conduction band electrons induced by interaction with an electromagnetic field. This resonance is called Surface Plasmon Resonance (SPR).
Figure: Schematic of plasmon oscillation for a sphere, showing the displacement of the conduction electron charge cloud relative to the nuclei.

15. Optical Properties of Gold Nanorods
Gold nanorods have shape and size-dependent optical properties originating from anisotropic shape and tunable aspect ratio.
Nikoobakht et al. Chem Mater. 2003, 15,
Aspect Ratio (AR) = L/W L W

16. Gold Nanorods
Under electromagnetic field of light, the conduction band electrons undergo a collective coherent oscillation in resonance with the frequency of the incident light. This is known as the localized surface plasmon resonance (LSPR).
Due to their anisotropic shape, 2 extinction peaks can be observed from gold nanorods.
Huang et al. Adv Mater. 2009, 21,

17. A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods
GNR (25 x 65 nm) UV-Vis absorption spectra (normalized) and TEM image

18. Head & Neck Cancer Cell Au

19. Tumor detection based on DR measurements of targeted gold nanorods (GNR)
Enhancing the tumor absorption coefficient by EFGR labeled GNR injection.
650 nm
Tumor µa
650 nm
Diffusion Reflection measurements

20. Diffusion reflection decreases faster due to GNRs accumulation6 -6
GNRs injection

21. Tumor detection based on DR of targeted gold nanorods (GNR)
The tumor presents a slope different from the normal tissue’s slope even more than 20 hours post injection.
Ankri et.al; A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods, International journal of Nanomedicine, 2012

22. Different absorption coefficients
Expected µa (mm-1)
Slope2
Experimental µa (mm-1)
0.0123
0.011±0.006
0.012±0.0007
0.0132
0.0143±0.003
0.0131±0.0031
0.0152
0.0256±0.003
0.0146±0.0007
0.0216
0.0625±0.004
0.0229±0.001
0.0312
0.137±0.0016
0.0397±0.0004
0.0986
0.42±0.001
0.104±0.0002
GNR exntinction coefficient
1 ml/mg*mm

23. a quantitative study, Journal of Biophotonics, 2012
Calculating tumor GNR concentration from the DR profile in-vivo
FAA spectroscopy
GNR conc. in tumor =
Time
(∆Slope)2
GNR concentration (mg/ml)
Before GNR injection
t=15 min post GNR injection
t= 5 h post GNR injection
0.0036
0.0096
t= 10 h post GNR injection
0.0275
0.015
EGFR- targeted
Ankri et.al; In-vivo tumor detection using diffusion reflection measurements of targeted gold nanorods-
a quantitative study, Journal of Biophotonics, 2012

24. DR measurements of high concentrations of GNR-
a Red shift is observed
Dark field Microscopy:
GNR with different densities

25. a spectral broadening is observedλ0 ∆λ
DR measurements of tumor bearing mice with different concentrations of targeted GNR-
a spectral broadening is observed
Ankri et.al; Intercoupling surface plasmon resonance and diffusion reflection measurements for real-time cancer detection, Journal of Biophotonics, 2012

26. NEJM Dec 2013
The Aim: To develop a new, easy to use, and non-invasive method at low cost, to locate atherosclerotic vascular disease at its early stages, particularly unstable plaques with ongoing inflammation prone to rupture

27. Stable vs. Unstable (vulnerable) Plaques
Rich in macrophages, foam cells,
inflammatory cells, thin fibrous cap
Rich in extracellular matrix
smooth muscle cells, thick cap

28. Macrophages before incubation with GNRs
Macrophages+ GNRs 0.02 mg/ml
Macrophages+ GNRs 0.2 mg/ml

29. Macrophages +/-GNRs
Homogenous and GNRs

30. In Vivo ; Rat injury MODEL
A cross-section of a rat balloon-injured carotid artery 2 weeks post-injury stained with hematoxylin and eosin (H&E) clearly depicts cellular-rich neointima development. Magnification is 100x for the large photomicrograph. A right carotid artery B left injured carotid artery

31. First in vivo DR measurements of atherosclerosis with GNR

32. 3D CT Artery imaging