Fluorescence attenuated by a thick scattering medium: Theory, simulations and experiments.

Fluorescence-based imaging has an enormous impact on our understanding of biological systems. However, in vivo fluorescence imaging is greatly influenced by tissue scattering. A better understanding of this dependence can improve the potential of noninvasive in vivo fluorescence imaging. In this article, we present a diffusion model, based on an existing master-slave model, of isotropic point sources imbedded in a scattering slab, representing fluorophores within a tissue. The model was compared with Monte Carlo simulations and measurements of a fluorescent slide measured through tissue-like phantoms with different reduced scattering coefficients (0.5-2.5 mm-1 ) and thicknesses (0.5-5 mm). Results show a good correlation between our suggested theory, simulations and experiments; while the fluorescence intensity decays as the slab's scattering and thickness increase, the decay rate decreases as the reduced scattering coefficient increases in a counterintuitive manner, suggesting fewer fluorescence artifacts from deep within the tissue in highly scattering media.

A Novel Facial Cream Based on Skin-penetrable Fibrillar Collagen Microparticles.

Background: Collagen protein plays a notable role maintaining firm skin. Topical creams containing collagen fibers are widely available, but their usefulness is questionable due to limited skin penetration. When applied in a cream, collagen does not penetrate the skin leaving the skin structure unaffected. Objective: We formulated micronized collagen in a cream base. Using human skin samples, we sought to investigate the ability of the micronized collagen cream to penetrate human skin. Methods: Particle sizes of micronized marine collagen were evaluated using electron microscopy. Optical profilometry was conducted to evaluate skin topography and roughness. The antioxidant activity of the collagen was evaluated using the electron paramagnetic resonance technique by measuring the changes in free radical production. Collagen penetration depth in human skin samples was monitored using a non-invasive optical technique known as iterative multiplane optical property extraction, which works based on the detection of laser light phase changes following the presence of collagen particles in deep skin layers. Results: According to the electron microscopy, collagen particles were found to be of various sizes, the smallest being about 120nm in diameter. Skin topography measurements revealed that the treated collagen cream increased skin smoothness of the samples. Our results derived from the iterative multiplane optical property extraction indicated that micronized collagen in a cream base penetrates both the stratum corneum and the deep epidermal layers toward the dermis. Conclusion: Our investigation suggests that the collagen in the studied cream formulation was able to penetrate the stratum coreum and deep epidermal layers in human skin samples.

Iterative optical technique for detecting anti-leishmania nanoparticles in mouse lesions.

Nanoparticles (NPs) based drugs for topical administration are gaining interest in the biomedical world. However, a study tool of their penetration depth to the different tissue layers without additional markers or contrast agents is required in order to relieve safety concerns. While common diagnostic tools, e.g. X-ray, computed tomography or magnetic resonance imaging, can provide in vivo detection of the metallic NPs, their resolution cannot determine the exact penetration depth to the thin skin layers. In this work, we propose the noninvasive nanophotonics iterative multi-plane optical property extraction (IMOPE) technique for the novel iron-based NPs detection in leishmaniasis lesions. The optical properties of the different tissue layers: epidermis, dermis, subcutaneous fat and muscle, were examined before and after topical drug administration. The potential topical drug was detected in the epidermis (∼13µm) and dermis (∼160µm) layers in mice lesions at different stages of the disease (two or four weeks post infection). The lesion size influence on the detection was also observed, where in larger lesions the IMOPE senses a greater presence of the topical drug.

Effect of optical magnification on the detection of the reduced scattering coefficient in the blue regime: theory and experiments.

Imaging 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 technique. It analyzes the reconstructed reemitted light phase image. The root mean square of the phase image yields two graphs with opposite behaviors that intersect at µ's,cp. These graphs enable the extraction of a certain range of the reduced scattering coefficient, µ's. Here, we aim to extend the range of µ's 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 tested experimentally, showing that the technique can be adapted to different ranges of µ's by changing the magnification.

Media Characterization under Scattering Conditions by Nanophotonics Iterative Multiplane Spectroscopy Measurements.

Characterizing materials is preferably done by multiple wavelengths. In opaque materials, the scattering poses a challenge due to the additional complexity to the spectroscopic measurements. We have previously demonstrated an iterative multiplane method for characterizing materials using the reflection from turbid media. Initial studies were performed in the red wavelength regime (632.8 nm) which is optimal for biomedical applications. However, in order to differentiate between materials, it is better to use multiple wavelengths, as spectroscopy may detect the material fingerprint. In this paper, our iterative multiplane optical property extraction (IMOPE) technique is presented in the blue regime (473 nm). Agar-based solid phantom measurements were conducted and compared to our theoretical model. Compatibility between experiments in the red and blue wavelengths shows the robustness of our technique.

Algorithm for in vivo detection of tissue type from multiple scattering light phase images.

In vivo physiological assessments are typically done by either imaging techniques or by sensing changes in the attenuation coefficient. Using visible or near-infrared (NIR), imaging is mainly possible for thin tissues. On the other hand, clinical information can also be detected by examining changes in tissue optical properties. The most challenging aspect in sensing techniques is the spectral dependent scattering, which varies with the physiological state and tissue type. We have previously published our novel noninvasive nanophotonics technique for detecting tissue scattering based on reflectance measurements: the iterative multi-plane optical property extraction (IMOPE). The IMOPE reconstructs the reemitted light phase using an iterative algorithm and extracts the scattering properties based on a theoretical model. This paper presents the in vivo application of distinguishing between different mouse tissue areas. The reconstructed phase images reveal different areas in the inner thigh of a mouse, which are related to the muscle, bone, and skin. The IMOPE uses the reconstructed phases for sensing and detecting unseen components beneath the skin surface. This technique could be further applied to the diagnosis of various physiological states.

Topical Hyaluronic Acid Facial Cream with New Micronized Molecule Technology Effectively Penetrates and Improves Facial Skin Quality: Results from In-vitro, Ex-vivo, and In-vivo (Open-label) Studies.

Background: Topical hyaluronic acid (HA) has shown effectiveness in maintaining skin hydration. Topical creams containing HA are widely available, but their efficacy is limited by their lack of penetration into the skin due to the large molecule size of HA, the result of being formulated into a cream base. Objective: In this three-part study (in vitro, ex vivo, and in vivo), molecule sizes, penetration levels, and antiaging qualities of a topical HA facial cream that was formulated using a new technology that micronizes HA molecules (m-HA) were assessed. Methods and Results: Particle sizes of m-HA were evaluated using electron microscopy, which showed varying sizes, the smallest of which was 100nm in diameter. The antioxidation capabilities of m-HA were measured using electron spin resonance and were found to be higher than original HA. Skin penetration of the m-HA formulation was evaluated via immunohistochemical staining of porcine skin samples, which demonstrated penetration of the formulation into the stratum corneum and the deep epidermal layers toward the dermis. Antiaging qualities of the m-HA formulation were assessed in an open-label clinical study that included 36 healthy adult women. Skin parameters were measured objectively (e.g., Corneometer, Cutometer) and subjectively via patient questionnaire, results of which indicated significant improvements in facial skin hydration, elasticity, and wrinkle depth. Conclusion: The topical HA facial cream with m-HA technology demonstrated penetration into the epidermal skin layer, and, to our knowledge, our formulation is the first HA facial cream to achieve this. Clinical application of the facial cream demonstrated objective and subjective improvements in facial skin quality of healthy adult female subjects. Our results support the use of this new HA facial cream with m-HA technology as an effective antiaging topical therapy. Larger randomized, controlled studies are needed to confirm our findings.

Optical method to extract the reduced scattering coefficient from tissue: theory and experiments.

Tissues are considered challenging in terms of structure and composition analysis due to their tendency to multiple scatter the incident light. One of the most common theories for extracting optical properties of tissue is diffusion reflection (DR). In this Letter, we propose a new paradigm for estimating the reduced scattering coefficient of a medium from the reflected light phase. The technique is a modified DR theory wherein the phase is calculated by the product of the wavenumber and the average pathlength. This theory is supported by the reconstructed phase of tissue-like phantom experiments from an iterative algorithm.

[CONCISE NANOMEDICINE REVIEW].

INTRODUCTION: Nanomedicine is a rapidly evolving medical domain utilizing 1-100nm nanoscale particles to achieve medical goals in either one or more medical aspects - diagnosis, imaging and therapy. Nanomedicine employs a combination of methods stemming from life and exact sciences. This review deals briefly with the principles behind the scenes guiding the design, manufacture and employment of these nanoparticles. Some representative examples of the various applications are provided from the abundance of existing nanoparticles. The main topics discussed are those related to composition, characteristics of nanoparticles, usage in cancer, drug delivery and various central nervous system applications. Possible toxicity and future teratogenicity research pertaining to nanoparticles are also elaborated upon.

Improved Margins Detection of Regions Enriched with Gold Nanoparticles inside Biological Phantom.

Utilizing the surface plasmon resonance (SPR) effect of gold nanoparticles (GNPs) enables their use as contrast agents in a variety of biomedical applications for diagnostics and treatment. These applications use both the very strong scattering and absorption properties of the GNPs due to their SPR effects. Most imaging methods use the light-scattering properties of the GNPs. However, the illumination source is in the same wavelength of the GNPs' scattering wavelength, leading to background noise caused by light scattering from the tissue. In this paper we present a method to improve border detection of regions enriched with GNPs aiming for the real-time application of complete tumor resection by utilizing the absorption of specially targeted GNPs using photothermal imaging. Phantoms containing different concentrations of GNPs were irradiated with a continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms. By modulating the laser illumination, and use of a simple post processing, the border location was identified at an accuracy of better than 0.5 mm even when the surrounding area got heated. This work is a continuation of our previous research.

New optical sensing technique of tissue viability and blood flow based on nanophotonic iterative multi-plane reflectance measurements.

Physiological substances pose a challenge for researchers since their optical properties change constantly according to their physiological state. Examination of those substances noninvasively can be achieved by different optical methods with high sensitivity. Our research suggests the application of a novel noninvasive nanophotonics technique, ie, iterative multi-plane optical property extraction (IMOPE) based on reflectance measurements, for tissue viability examination and gold nanorods (GNRs) and blood flow detection. The IMOPE model combines an experimental setup designed for recording light intensity images with the multi-plane iterative Gerchberg-Saxton algorithm for reconstructing the reemitted light phase and calculating 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. We have demonstrated this new concept of correlating the light phase STD and the optical properties of a substance, using transmission measurements only. This paper presents, for the first time, 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).

Enhanced pharmacological activity of vitamin B12 and penicillin as nanoparticles.

Sonochemistry has become a well-known technique for fabricating nanomaterials. Since one of the advantages of nanomaterials is that they have higher chemical activities compared with particles in the bulk form, efforts are being made to produce nano organic compounds with enhanced biological activities that could be exploited in the medical area. This study uses the sonication technique to prepare nano Vitamin B12 and nano Penicillin, and demonstrates their enhanced biological and pharmacological activity. The size and morphology of the nano Penicillin and nano Vitamin B12 were investigated using electron microscopy as well as dynamic light scattering techniques. The sizes of Penicillin and Vitamin B12 nanoparticles (NPs) were found to be 70 and 120-180 nm, respectively. The bactericidal effect of nano Penicillin was studied and found to be higher than that of the bulk form. Reducing the size of Vitamin B12 resulted in their enhanced antioxidative activity as observed using the electron paramagnetic spectroscopy technique. The penetration depth of these organic NPs can be detected by an optical iterative method. It is believed that nano organic drugs fabrication will have a great impact on the medical field.

Detecting concentrations of milk components by an iterative optical technique.

This paper introduces a theoretical and practical model for reconstructing the scattering properties of a participating media. Our theory is based on a robust generalization of the Gerchberg-Saxton (G-S) algorithm. At the end of this algorithm the reduced scattering coefficient µ's of a given substance, can be estimated from the standard deviation (STD) of the retrieved phase of the remitted light. We use the theory to compute the phase's STD that directly correlated to the optical properties for different types of milk components, and we derive a novel appearance model for milk parameterized by the lactose and protein contents. Our results show that we are able to detect the possibility of lactose and milk proteins' quantitative signature by the G-S optical tool, en route to the design of a novel milk-content-monitoring tool. Sketch of the experimental setup for light intensity measurements and reduced scattering coefficient reconstruction. The samples were prepared from various milk components: whey protein, sodium casienate and lactose, at different concentrations.

Detecting nanoparticles in tissue using an optical iterative technique.

Determining the physical penetration depth of nanoparticles (NPs) into tissues is a challenge that many researchers have been facing in recent years. This paper presents a new noninvasive method for detecting NPs in tissue using an optical iterative technique based on the Gerchberg-Saxton (G-S) algorithm. At the end of this algorithm the reduced scattering coefficient (µs'), of a given substance, can be estimated from the standard deviation (STD) of the retrieved phase of the remitted light. Presented in this paper are the results of a tissue simulation which indicate a linear ratio between the STD and the scattering components. A linear ratio was also observed in the tissue-like phantoms and in ex vivo experiments with and without NPs (Gold nanorods and nano Methylene Blue). The proposed technique is the first step towards determining the physical penetration depth of NPs.