Spatially offset Raman spectroscopy for bone strength prediction.

Bone strength is a worldwide health concern. Although multiple techniques have been developed to evaluate bone quality, there are still gaps to be filled. Here we report a non-invasive approach for the prediction of bone strength using spatially offset Raman spectroscopy.

Full depth measurement of tenofovir transport in rectal mucosa using confocal Raman spectroscopy and optical coherence tomography.

The prophylactic activity of antiretroviral drugs applied as microbicides against sexually transmitted HIV is dependent upon their concentrations in infectable host cells. Within mucosal sites of infection (e.g.

Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography.

Vaginally applied microbicide products offer a female-controlled strategy for preventing sexual transmission of HIV. Microbicide transport processes are central to their functioning, and there is a clear need for a better understanding of them. To contribute to that end, we developed an assay to analyze mass transport rates of microbicide molecules within the epithelial and stromal layers of polarized vaginal mucosal tissue during contact with a gel vehicle.

Dual-axis optical coherence tomography for deep tissue imaging.

We have developed dual-axis optical coherence tomography (DA-OCT) which enables deep tissue imaging by using a novel off-axis illumination/detection configuration. DA-OCT offers a 100-fold speed increase compared with its predecessor, multispectral multiple-scattering low coherence interferometry (ms2/LCI), by using a new beam scanning mechanism based on a microelectro-mechanical system (MEMS) mirror. The data acquisition scheme was altered to take advantage of this scanning speed, producing tomographic images at a rate of 4 frames (B-scans) per second.

Sensitivity of spatially offset Raman spectroscopy (SORS) to subcortical bone tissue.

The development of spatially offset Raman spectroscopy (SORS) has enabled deep, non-invasive chemical characterization of turbid media. Here, we use SORS to measure subcortical bone tissue and depth-resolved biochemical variability in intact, exposed murine bones. We also apply the technique to study a mouse model of the genetic bone disorder osteogenesis imperfecta.

Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy.

Confocal Raman spectroscopy was implemented in a new label-free technique to quantify molecular diffusion coefficients within gels. A leading anti-HIV drug, tenofovir, was analyzed in a clinical microbicide gel. The gel was tested undiluted, and in 10%-50% wt/wt dilutions with vaginal fluid simulant to capture the range of conditions likely occurring in vivo.

Evaluation of burn severity in vivo in a mouse model using spectroscopic optical coherence tomography.

Clinical management of burn injuries depends upon an accurate assessment of the depth of the wound. Current diagnostic methods rely primarily on subjective visual inspection, which can produce variable results. In this study, spectroscopic optical coherence tomography was used to objectively evaluate burn injuries in vivo in a mouse model.

Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue.

We report the development of a combined confocal Raman spectroscopy (CRS) and optical coherence tomography (OCT) instrument (CRS-OCT) capable of measuring analytes in targeted biological tissues with sub-100-micron spatial resolution. The OCT subsystem was used to measure depth-resolved tissue morphology and guide the acquisition of chemically-specific Raman spectra. To demonstrate its utility, the instrument was used to accurately measure depth-resolved, physiologically-relevant concentrations of Tenofovir, a microbicide drug used to prevent the sexual transmission of HIV, in ex vivo tissue samples.

Functional optical coherence tomography: principles and progress.

In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues.

Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid biological tissue and tissue-simulating phantoms.

Traditional slit-based spectrometers have an inherent trade-off between spectral resolution and throughput that can limit their performance when measuring diffuse sources such as light returned from highly scattering biological tissue. Recently, multielement fiber bundles have been used to effectively measure diffuse sources, e.g.

In vivo analysis of burns in a mouse model using spectroscopic optical coherence tomography.

Spectroscopic analysis of biological tissues can provide insight into changes in structure and function due to disease or injury. Depth-resolved spectroscopic measurements can be implemented for tissue imaging using optical coherence tomography (OCT). Here, spectroscopic OCT is applied to in vivo measurement of burn injury in a mouse model.

Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones.

Clinical diagnoses of bone health and fracture risk typically rely on measurements of bone density or structure, but the strength of a bone is also dependent on its chemical composition. Raman spectroscopy has been used extensively in ex vivo studies to measure the chemical composition of bone. Recently, spatially offset Raman spectroscopy (SORS) has been utilized to measure bone transcutaneously.

Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis.

Clinical prediction of bone fracture risk primarily relies on measures of bone mineral density (BMD). BMD is strongly correlated with bone strength, but strength is independent of fracture toughness, which refers to the bone's resistance to crack initiation and propagation. In that sense, fracture toughness is more relevant to assessing fragility-related fracture risk, independent of trauma.

Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling.

Background: Exposure to lead (Pb) from environmental and industrial sources remains an overlooked serious public health risk. Elucidating the effect of Pb on bone cell function is therefore critical for understanding its risk associated with diseases of low bone mass.

Objectives: We tested the hypothesis that Pb negatively affects bone mass.

Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk.

Objective: Glucocorticoid (GC) therapy is associated with increased risk of fracture in patients with rheumatoid arthritis (RA). To elucidate the cause of this increased risk, we examined the effects of chronic erosive inflammatory arthritis and GC treatment on bone quality, structure, and biomechanical properties in a murine model.

Methods: Mice with established arthritis and expressing human tumor necrosis factor α (TNFα) transgene (Tg) and their wild-type (WT) littermates were continually treated with GC (prednisolone 5 mg/kg/day via subcutaneous controlled-release pellet) or placebo for 14, 28, or 42 days.

Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis.

Although glucocorticoids are frequently prescribed for the symptomatic management of inflammatory disorders such as rheumatoid arthritis, extended glucocorticoid exposure is the leading cause of physician-induced osteoporosis and leaves patients at a high risk of fracture. To study the biochemical effects of glucocorticoid exposure and how they might affect biomechanical properties of the bone, Raman spectra were acquired from ex vivo tibiae of glucocorticoid- and placebo-treated wild-type mice and a transgenic mouse model of rheumatoid arthritis. Statistically significant spectral differences were observed due to both treatment regimen and mouse genotype.

Determination of ideal offset for spatially offset Raman spectroscopy.

A key design parameter in spatially offset Raman spectroscopy (SORS) is the choice of offset distance between the illumination and collection areas. To investigate this choice, we performed SORS measurements on a simple two-layer chemical phantom. We show that while the SORS ratio, or the ratio of signal from the bottom layer to the top layer, monotonically increases with spatial offset, the signal-to-noise ratio (SNR) does not.