Fiber-based polarization-sensitive Mueller-matrix optical coherence tomography with continuous source polarization modulation

A novel fiber-based Mueller-matrix optical coherence tomography system is demonstrated for acquiring polarization images of biological tissues in vivo. The system features a single broadband source, a rapid scanning optical delay line, and an electro-optical polarization modulator that modulates the polarization states of the source light continuously. A frame of a 200 by 1515 pixel 2D image can be acquired in half a second. The Jones matrix of a sample is calculated from two frequency components--the A-scan carrier frequency component and the beat frequency component between the modulation frequency and the carrier frequency. For samples having negligible diattenuation, the Jones matrix can be calculated from a single measurement of either the horizontal or the vertical interference signal. The system was first validated by imaging standard polarization elements and then applied to imaging biological samples

Characterization of the polarization properties of biological tissues with fiber-based Mueller-matrix optical coherence tomography

A fast scanning fiber-based system of Mueller-matrix optical coherence tomography was built to characterize the polarization properties of biological tissues with high spatial resolution. A polarization modulator with its fast-axis oriented at 45° in the source arm of the Michelson interferometer, driven by a sinusoidal wave, was used to continuously modulate the incident polarization states of both the sample and the reference arms. Two detection channels were used to detect the horizontal and vertical polarization components of the interference signals, which were used to calculate the roundtrip Jones matrix of the sample. The roundtrip polarization parameters of the sample were calculated from the measured Jones matrix. The system was successfully tested for both standard optical polarization elements and various types of biological samples

In vivo burn imaging using Mueller optical coherence tomography

We report on the use of a high-speed, fiber-based Mueller-matrix optical coherence tomography system with continuous source-polarization modulation for in vivo burn depth evaluation and healing monitoring. A homemade hand-held probe with integrated optical scanning and beam delivering optics was coupled in the sample arm. In vivo burn imaging was demonstrated on porcine skin at different stages of the wound healing process, where porcine skin was used because of its similarity to the human skin. Thermally damaged region was clearly localized in the depth-resolved phase retardation image extracted from the measured Jones matrix. The burn areas in the OCT images agreed well with the histology. By using a decomposition algorithm developed by our group, we also mapped the local birefringence of the skin. The experimental results demonstrate the system’s potential for in vivo burn-depth determination

Burn depth determination using high-speed polarization-sensitive Mueller optical coherence tomography with continuous polarization modulation

National Health Interview Survey (NHIS) estimates more than 1.1 million burn injuries per year in the United States, with nearly 15,000 fatalities from wounds and related complications. An imaging modality capable of evaluating burn depths non-invasively is the polarization-sensitive optical coherence tomography. We report on the use of a high-speed, fiber-based Mueller-matrix OCT system with continuous source-polarization modulation for burn depth evaluation. The new system is capable of imaging at near video-quality frame rates (8 frames per second) with resolution of 10 μm in biological tissue (index of refraction: 1.4) and sensitivity of 78 dB. The sample arm optics is integrated in a hand-held probe simplifying the in vivo experiments. The applicability of the system for burn depth determination is demonstrated using biological samples of porcine tendon and porcine skin. The results show an improved imaging depth (1 mm in tendon) and a clear localization of the thermally damaged region. The burnt area determined from OCT images compares well with the histology, thus proving the system's potential for burn depth determination

Characterization of the polarization properties of biological tissues with fiber-based Mueller-matrix optical coherence tomography

A fast scanning fiber-based system of Mueller-matrix optical coherence tomography was built to characterize the polarization properties of biological tissues with high spatial resolution. A polarization modulator with its fast-axis oriented at 45° in the source arm of the Michelson interferometer, driven by a sinusoidal wave, was used to continuously modulate the incident polarization states of both the sample and the reference arms. Two detection channels were used to detect the horizontal and vertical polarization components of the interference signals, which were used to calculate the roundtrip Jones matrix of the sample. The roundtrip polarization parameters of the sample were calculated from the measured Jones matrix. The system was successfully tested for both standard optical polarization elements and various types of biological samples

Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury initiates biochemical processes that lead to secondary neurodegeneration. Imaging studies suggest that tissue loss may continue for months or years after traumatic brain injury in association with chronic microglial activation. Recently we found that metabotropic glutamate receptor 5 (mGluR5) activation by (<it>RS</it>)-2-chloro-5-hydroxyphenylglycine (CHPG) decreases microglial activation and release of associated pro-inflammatory factors <it>in vitro</it>, which is mediated in part through inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Here we examined whether delayed CHPG administration reduces chronic neuroinflammation and associated neurodegeneration after experimental traumatic brain injury in mice.</p> <p>Methods</p> <p>One month after controlled cortical impact traumatic brain injury, C57Bl/6 mice were randomly assigned to treatment with single dose intracerebroventricular CHPG, vehicle or CHPG plus a selective mGluR5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine. Lesion volume, white matter tract integrity and neurological recovery were assessed over the following three months.</p> <p>Results</p> <p>Traumatic brain injury resulted in mGluR5 expression in reactive microglia of the cortex and hippocampus at one month post-injury. Delayed CHPG treatment reduced expression of reactive microglia expressing NADPH oxidase subunits; decreased hippocampal neuronal loss; limited lesion progression, as measured by repeated T2-weighted magnetic resonance imaging (at one, two and three months) and white matter loss, as measured by high field <it>ex vivo </it>diffusion tensor imaging at four months; and significantly improved motor and cognitive recovery in comparison to the other treatment groups.</p> <p>Conclusion</p> <p>Markedly delayed, single dose treatment with CHPG significantly improves functional recovery and limits lesion progression after experimental traumatic brain injury, likely in part through actions at mGluR5 receptors that modulate neuroinflammation.</p

Innate Synchronous Oscillations in Freely-Organized Small Neuronal Circuits

BACKGROUND: Information processing in neuronal networks relies on the network's ability to generate temporal patterns of action potentials. Although the nature of neuronal network activity has been intensively investigated in the past several decades at the individual neuron level, the underlying principles of the collective network activity, such as the synchronization and coordination between neurons, are largely unknown. Here we focus on isolated neuronal clusters in culture and address the following simple, yet fundamental questions: What is the minimal number of cells needed to exhibit collective dynamics? What are the internal temporal characteristics of such dynamics and how do the temporal features of network activity alternate upon crossover from minimal networks to large networks? METHODOLOGY/PRINCIPAL FINDINGS: We used network engineering techniques to induce self-organization of cultured networks into neuronal clusters of different sizes. We found that small clusters made of as few as 40 cells already exhibit spontaneous collective events characterized by innate synchronous network oscillations in the range of 25 to 100 Hz. The oscillation frequency of each network appeared to be independent of cluster size. The duration and rate of the network events scale with cluster size but converge to that of large uniform networks. Finally, the investigation of two coupled clusters revealed clear activity propagation with master/slave asymmetry. CONCLUSIONS/SIGNIFICANCE: The nature of the activity patterns observed in small networks, namely the consistent emergence of similar activity across networks of different size and morphology, suggests that neuronal clusters self-regulate their activity to sustain network bursts with internal oscillatory features. We therefore suggest that clusters of as few as tens of cells can serve as a minimal but sufficient functional network, capable of sustaining oscillatory activity. Interestingly, the frequencies of these oscillations are similar those observed in vivo

Global Gene Expression Profiling Of Human Pleural Mesotheliomas: Identification of Matrix Metalloproteinase 14 (MMP-14) as Potential Tumour Target

BACKGROUND:The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. METHODOLOGY:We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002). CONCLUSIONS:Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma