Rinat Ankri

In‐vivo Tumor detection using diffusion reflection measurements of targeted gold nanorods – a quantitative study

The ability to quantitatively and non-invasively detect nanoparticles has important implications on their development as an in-vivo cancer diagnostic tool. The Diffusion Reflection (DR) method is a simple, non-invasive imaging technique which has been proven useful for the investigation of tissues optical parameters. In this study, Monte Carlo (MC) simulations, tissue-like phantom experiments and in-vivo measurements of the reflected light intensity from tumor bearing mice are presented. Following intravenous injection of antibody conjugated poly (ethylene glycol)-coated (PEGylated) gold nanorods (GNR) to tumor-bearing mice, accumulation of GNR in the tumor was clearly detected by the DR profile of the tumor. The ability of DR measurements to quantitate in-vivo the concentration of the GNR in the tumor was demonstrated and validated with Flame Atomic Absorption spectroscopy results. With GNR as absorbing contrast agents, DR has important potential applications in the image guided therapy of superficial tumors such as head and neck cancer, breast cancer and melanoma.

A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods

This paper presents a new method for cancer detection based on diffusion reflection measurements. This method enables discrimination between cancerous and noncancerous tissues due to the intense light absorption of gold nanorods (GNRs), which are selectively targeted to squamous cell carcinoma head and neck cancer cells. Presented in this paper are tissue-like phantom and in vivo results that demonstrate the high sensitivity of diffusion reflection measurements to the absorption differences between the GNR-targeted cancerous tissue and normal, noncancerous tissue. This noninvasive and nonionizing optical detection method provides a highly sensitive, simple, and inexpensive tool for cancer detection.

Reflected light intensity profile of two-layer tissues: phantom experiments

Experimental measurements of the reflected light intensity from two-layer phantoms are presented. We report, for the first time, an experimental observation of a typical reflected light intensity behavior for the two-layer structure characterized by two different slopes in the reflected light profile of the irradiated tissue. The point in which the first slope changes to the second slope, named as the crossover point, depends on the upper layer thickness as well as on the ratio between the absorption coefficients of the two layers. Since similar experiments from one-layer phantoms present a monotonic decay behavior, the existence and the location of the crossover point can be used as a diagnostic fingerprint for two-layer tissue structures. This pertains to two layers with greater absorptivity in the upper layer, which is the typical biological case in tissues like skin.

Errata: Subcutaneous gold nanorods detection with diffusion reflection measurement

Abstract. The ability to quantitatively and noninvasively detect nanoparticles nearby the skin surface has important implications on their development as an in vivo cancer diagnostic tool. The diffusion reflection (DR) method is a simple, noninvasive imaging technique which has been proven useful for the investigation of the optical parameters of the tissue. A new method is presented for the measurements of gold nanorod (GNR) concentration in tissue-like phantoms, based on DR measurement and intense light absorption of GNR. Monte Carlo simulations and tissue-like phantom measurements of the reflected light intensity are presented. The ability to extract optical properties of phantoms and their GNR concentrations from DR measurements is demonstrated, followed by a discussion about the best mathematical model for light propagation in tissues, based on the diffusion theory.

Estimation of the Optimal Wavelengths for Laser-Induced Wound Healing

According to earlier in vitro low level laser therapy (LLLT) studies, wavelengths in the red and near infrared range, that are absorbed by cytochrome oxidase, stimulate cell growth and hence wound healing. Wavelengths in the blue region that are absorbed by flavins were found to exert a bactericidal effect that is very important for treating infected wounds. However, as far as therapeutic application of light is concerned, penetration into the tissue must be considered. For this purpose we estimated the penetration depth as a function of the relevant wavelengths, using the formulae of the photon migration model for skin tissue.

Gold nanorods as absorption contrast agents for the noninvasive detection of arterial vascular disorders based on diffusion reflection measurements.

In this study we report the use of gold nanorods (GNRs) as absorption contrast agents in the diffusion reflection (DR) method for the in vivo detection of atherosclerotic injury. The early detection and characterization of atherosclerotic vascular disease is considered to be one of the greatest medical challenges today. We show that macrophage cells, which are major components of unstable active atherosclerotic plaques, uptake gold nanoparticles, resulting in a change in the optical properties of tissue-like phantoms and a unique DR profile. In vivo DR measurements of rats that underwent injury of the carotid artery showed a clear difference between the DR profiles of the injured compared with healthy arteries. The results suggest that DR measurements following GNRs administration represent a potential novel method for the early detection of atherosclerotic vascular disease.

Intercoupling surface plasmon resonance and diffusion reflection measurements for real-time cancer detection.

Spatial diffusion reflection (DR) measurements of gold nanorods (GNR) were recently suggested as a simple and highly sensitive non-invasive and non-ionizing method for real-time cancer detection. In this paper we demonstrate that wavelength dependent DR measurements enable the spectral red-shift observation of highly concentrated GNR. By conjugating targeting moieties to the GNR, large density of GNR can specifically home onto cancer cells. The inter-particle plasmon resonance pattern of the highly concentrated GNR leads to an extension and a red-shift (Δλ) in the absorption spectrum of the concentrated GNR. Dark-field microscopy was used in order to measure the expected Δλ in different GNR concentrations in vitro. Double-wavelength DR measurements of tissue-like phantoms and tumor bearing mice containing different GNR concentrations are presented. We show that the DR profile of the highly concentrated GNR directly correlate with the spectral extension and red-shift. This presented work suggests that wavelength dependent DR method can serve as a promising tool for real-time superficial tumor detection.

Determination of coherence length in biological tissues

Lately in phototherapy the use of diodes instead of lasers was suggested for economical and practical reasons. It has been argued that lasers have no preference over diodes since they lose their coherence once penetrating biological tissues. However, this point has never been experimentally proven. In this work we, for the first time, have experimentally validated the conditions affecting the spatial coherence of a laser illumination going through a biological tissue.

Visible light induces no formation in sperm and endothelial cells

Visible light‐based stimulation using low‐intensity lasers, LEDs, and broadband visible light devices has been recently introduced for therapy of human tissues in the absence of exogenous photosensitizers. Nitric oxide (NO) formation might be a potential mechanism for photobiomodulation because it is synthesized in cells by nitric oxide synthase (NOS), which contains both flavin and heme groups that absorb visible light. NO synthesis may also result from increased reactive oxygen species (ROS), which are found in various cell cultures following visible light illumination. NO is mainly known for inducing blood vessel dilation by endothelial cells, and in sperm cells NO is considered as an important agent in acrosome reaction and capacitation process, which are essential for successful fertilization.

On Phantom Experiments of the Photon Migration Model in Tissues

Light-tissue interaction is common in clinical treatments and medical research, therefore investigation of light path in irradiated tissues is of high importance. In this research, reflected light intensity measurements from different homogeneous phantoms, combined with numerical simulations, have been used for the investigation of phantoms absorption properties. Our results suggest a good fitting between the theoretical model and the random walk simulations, enabling the extraction of the lattice absorption parameter. Yet, as long as low scattering phantom experiments are concerned, the photon migration model does not provide an adequate description for the phantom absorption coefficient extraction.