Deep tissue imaging using visible light is challenging due to its turbid nature. Nevertheless, clinical information can be detected by sensing changes in the tissue’s optical properties with low spatial resolution. The most challenging aspect is the spectral dependent scattering, which varies with physiological state and tissue layer. In this paper, we present the multi-layer study of the reflection-based iterative multiplane optical property extraction (IMOPE) technique. The IMOPE is a noninvasive nanophotonics technique that detects medium scattering properties based on the reemitted light phase. The extracted scattering properties are used as indicators of the internal tissue information and the presence of additional nanoparticles (NPs) in it. The technique is a combination of a theoretical model, an experimental setup, and the phase retrieval Gerchberg-Saxton algorithm. The IMOPE experimental setup records light intensity images at different locations, in order to reconstruct the phase by the multi-plane GS algorithm. Once the phase distribution is reconstructed, its root mean square (RMS) is calculated and compared to a theoretical model for obtaining the reduced scattering coefficient. This work presents the study of single-layer and two-layer tissue-like phantoms and a new phase image analysis that provides detection of different scattering layers with 0.2mm-1 sensitivity at different depths, following layers up to 6mm thickness. The IMOPE with the new phase image analysis was applied for the detection of the novel iron-based NPs drug (Nano-Leish-IL) in mice leishmaniasis lesions, where it was detected in the epidermis (∼13μm) and dermis (∼160μm) at different stages of the disease.
Imaging inside a turbid media is range limited. In contrast, sensing the medium’s optical properties is possible in larger depths using the iterative multi-plane optical properties extraction (IMOPE) technique. It analyzes the reemitted light phase image reconstructed from the iterative multi-plane Gerchberg-Saxton (GS) algorithm. The root mean square (RMS) of the phase yields two graphs with opposite behaviors, that cross each other in μ's,cp. The graphs enable the extraction of the reduced scattering coefficient, μs', of the measured tissue. The IMOPE was originally developed for illumination of red wavelength and for biological applications and was extended to the blue regime of the electromagnetic field, which is applicable for underwater research. In this work, we aim to extend the range of μs' detection by optical magnification. We use a modified diffusion theory and show how μ's,cp shifts with the varying magnification. The theoretical results were then tested experimentally, using agar-based phantoms with varying scatterings coefficients.
The interaction of light with different materials has been studied for hundreds of years in various research fields e.g., material analysis, quantum physics, biomedical optics, etc.. This interaction is determined by the material's optical properties which are spectrally dependent. Spectroscopic methods examine the spectral dependence of the interaction, which reveals the material fingerprint. However, in opaque materials, their characterization is more complex and challenging due to the scattering. We have previously presented the iterative multi-plane optical property extraction (IMOPE) technique for characterizing materials using the reflection from turbid media. The reflection-based IMOPE, which estimates medium scattering properties, combines a theoretical model with an experimental setup and the multiple measurement GS algorithm. This technique was initially aimed for biomedical applications, where the red wavelengths are the desired radiation source due to higher penetration depths. However, as in spectroscopy, multiple wavelengths, rather than just one, can provide more accurate information about components within the sample. In this research, we introduce the spectral reflection-based IMOPE for extracting the reduced scattering coefficient of a medium in the blue regime.
In vivo physiological sensing is typically done either by imaging thin tissues or by examining changes in the attenuation coefficient. One known technique for thin tissue in vivo applications is the optical coherence tomography (OCT). However, deep tissue methods are usually based on diffusion reflection (DR), which correlates the optical properties to the reflected light intensity. The attenuation coefficient is composed of tissue absorption and scattering. We present a noninvasive nanophotonics technique, the iterative multi-plane optical property extraction (IMOPE) for extracting the scattering properties from a turbid medium. The reflectance-based IMOPE is most relevant for in vivo applications, hence, in this research we suggest a new theoretical description of phase accumulation in deep tissue, which is rarely mentioned in the literature, using a modified DR theory that represents the phase based on the effective pathlength. The IMOPE records multiple intensity images, reconstructs the phase using Gerchberg-Saxton (GS) algorithm. This algorithm is usually being used for beam shaping or phase reconstruction. We propose to calculate the phase second order moment to estimate the scattering. IMOPE experiments were conducted with tissue-like phantoms for calibration purposes, as well as ex vivo and in vivo measurement. The suggested technique was applied both in transmission and reflection mode. The transmission based IMOPE detected organic nanoparticles within tissues and the quantitative signature of milk components. The reflectance-based IMOPE was applied for tissue viability test and in vivo gold nanorods and blood flow detection.
Extracting optical parameters of turbid medium (e.g. tissue) by light reflectance signals is of great interest and has many applications in the medical world, life science, material analysis and biomedical optics. The reemitted light from an irradiated tissue is affected by the light's interaction with the tissue components and contains the information about the tissue structure and physiological state. In this research we present a novel noninvasive nanophotonics technique, i.e., iterative multi-plane optical property extraction (IMOPE) based on reflectance measurements. The reflectance based IMOPE was applied for tissue viability examination, detection of gold nanorods (GNRs) within the blood circulation as well as blood flow detection using the GNRs presence within the blood vessels. The basics of the IMOPE combine a simple experimental setup for recording light intensity images with an iterative Gerchberg–Saxton (G-S) algorithm for reconstructing the reflected light phase and computing its standard deviation (STD). Changes in tissue composition affect its optical properties which results in changes in the light phase that can be measured by its STD. This work presents reflectance based IMOPE tissue viability examination, producing a decrease in the computed STD for older tissues, as well as investigating their organic material absorption capability. Finally, differentiation of the femoral vein from adjacent tissues using GNRs and the detection of their presence within blood circulation and tissues are also presented with high sensitivity (better than computed tomography) to low quantities of GNRs (<3 mg).
Various techniques for recovering optical parameters were developed over the years. However each has its limitations, constraints and disadvantages (e.g. accuracy, computational speed, sample assembly, distinguishing between the different parameters, etc.). This research suggests an optical technique for extracting the reduced scattering coefficient (μs') of substances by examining the light transmission through or reflection from them. It uses the multiple planes Gerchberg- Saxton (G-S) algorithm to reconstruct the light phase created by the substance. At the end of the algorithm, μs' can be estimated from the standard deviation (STD) of the retrieved phase of the reemitted light. We will use the theory to compute the phase’s STD that directly correlated to the optical properties of different substances. Two possible applications for this technique, out of many others, are nanoparticles (NPs) penetration depth determination, for promoting topical medications, and detection of milk components quantitative signature as en route to milk content monitoring tool. For the former application, three materials were fabricated into NPs and all presented an activity enhancement with their size reduction. Then the NPs were applied on tissues and detected by our technique. For the latter, different milk content concentrations were examined resulting with different STD values suggesting it can be used as indicator for the milk component concentrations.
In recent years, infiltrating materials into the human body has become a great challenge many researches are facing. In medicine and cosmetics today, there are materials which are administrated to patients by injection only. The main challenge with topical medication is penetrating the skin barrier. The skin is an effective barrier between the body and the outside environment, which prevents foreign materials entering the body easily. However, reducing the size of the desired materials might help their skin penetration ability. Recently nanoparticles (NPs) are being evaluated for use in many fields like chemistry, biology, medicine, physics and optics. The technique used in this work for forming organic NPs (ONPs) is the application of sonic waves to an aqueous solution, known as sonochemistry. To investigate the physical penetration depth of ONPs into the human body, we first developed a novel optical technique for detecting NPs within tissues. The detection of NPs is done by the extraction and investigation of the reemitted light phase.
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