Journal of Innovative Optical Health Sciences最新文献

The three-dimensional (3D) mechanical response of the cornea to intraocular pressure (IOP) elevation has not been previously reported. In this study, we use an ultrasound speckle tracking technique to measure the 3D displacements and strains within the central 5.5 mm of porcine corneas during the whole globe inflation. Inflation tests were performed on dextran-treated corneas (treated with a 10% dextran solution) and untreated corneas. The dextran-treated corneas showed an inflation response expected of a thin spherical shell, with through-thickness thinning and in-plane stretch, although the strain magnitudes exhibited a heterogeneous spatial distribution from the central to more peripheral cornea. The untreated eyes demonstrated a response consistent with swelling during experimentation, with through-thickness expansion overriding the inflation response. The average volume ratios obtained in both groups was near 1 confirming general incompressibility, but local regions of volume loss or expansion were observed. These results suggest that biomechanical measurements in 3D provide important new insight to understand the mechanical response of ocular tissues such as the cornea.

Amyloidopathy is one of the most prominent hallmarks of Alzheimer's disease (AD), the leading cause of dementia worldwide, and is characterized by the accumulation of amyloid plaques in the brain parenchyma. The plaques consist of abnormal deposits mainly composed of an aggregation-prone protein fragment, β-amyloid 1-40/1-42, into the extracellular matrix. Brillouin microspectroscopy is an all-optical contactless technique that is based on the interaction between visible light and longitudinal acoustic waves or phonons, giving access to the viscoelasticity of a sample on a subcellular scale. Here, we describe the first application of micromechanical mapping based on Brillouin scattering spectroscopy to probe the stiffness of individual amyloid plaques in the hippocampal part of the brain of a β-amyloid overexpressing transgenic mouse. Correlative analysis based on Brillouin and Raman microspectroscopy showed that amyloid plaques have a complex structure with a rigid core of β-pleated sheet conformation (β-amyloid) protein surrounded by a softer ring-shaped region richer in lipids and other protein conformations. These preliminary results give a new insight into the plaque biophysics and biomechanics, and a valuable contrast mechanism for the study and diagnosis of amyloidopathy.

Previous studies have shown cost effectiveness and quality-of-life benefit of pneumatic compression therapy (PCT) for lymphedema. Insurers, such as the Centers for Medicare/Medicaid (CMS), however, desire visual proof that PCT moves lymph. Near-infrared fluorescence lymphatic imaging (NIRFLI) was used to visualize lymphatic anatomy and function in four subjects with primary and cancer treatment-related lymphedema (LE) of the lower extremities before, during, and after pneumatic compression therapy (PCT). Optically transparent and windowed PCT garments allowed visualization of lymph movement during single, one-hour PCT treatment sessions. Visualization revealed significant extravascular and lymphatic vascular movement of intradermally injected dye in all subjects. In one subject with sufficient patent lymphatic vessels to allow quantification of lymph pumping velocities and frequencies, these values were significantly increased during and after PCT as compared to pre-treatment values. Lymphatic contractile activity in patent lymphatic vessels occurred in concert with the sequential cycling of PCT. Direct visualization revealed increased lymphatic function, during and after PCT therapy, in all lymphedema-affected extremities. Further studies are warranted to assess the effects of PCT pressure and sequences on lymph uptake and movement.

Gold nanoparticles (AuNPs) could serve as potential radiotherapy sensitizers because of their exceptional biocompatibility and high-Z material nature; however, since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries, whether surface ligands can affect their radiosensitization has seldom been investigated in the radiosensitization of AuNPs. By conducting head-to-head comparison on radiosensitization of two kinds of ultrasmall (~2 nm) near-infrared (NIR) emitting AuNPs that are coated with zwitterionic glutathione and neutral polyethylene glycol (PEG) ligands, respectively, we found that zwitterionic glutathione coated AuNPs (GS-AuNPs) can reduce survival rates of MCF-7 cells under irradiation of clinically used megavoltage photon beam at low dosage of ~2.25 Gy. On the other hand, PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation, clearly indicating the key role of surface chemistry in radiosensitization of AuNPs. More detailed studies suggested that such difference was independent of cellular uptake and its efficiency, but might be related to the ligand-induced difference in photoelectron generation and/or interactions between AuNPs and X-ray triggered reactive oxygen species (ROS).

Purpose: To provide a geographical map of choroidal thickness (CT) around the macular region among subjects with low, moderate and high myopia.

Methods: 20 myopic subjects (n = 40 eyes) without other identified pathologies participated in this study: 20 eyes of ≤ 3 diopters (D) (low myopic), 10 eyes between -3 and -6D (moderate myopic), and 10 eyes of ≥ 6D (high myopic). The mean age of subjects was 30.2 years (± 7.6 years; range, 24 to 46 years). A 1050 nm spectral-domain optical coherence tomography (SD-OCT) system, operating at 120 kHz imaging rate, was used in this study to simultaneously capture 3D anatomical images of the choroid and measure intraocular length (IOL) in the subject. The 3D OCT images of the choroid were segmented into superior, inferior, nasal and temporal quadrants, from which the CT was measured, representing radial distance between the outer retinal pigment epithelium (RPE) layer and inner scleral border. Measurements were made within concentric regions centered at fovea centralis, extended to 5 mm away from fovea at 1 mm intervals in the nasal and temporal directions. The measured IOL was the distance from the anterior cornea surface to the RPE in alignment along the optical axis of the eye. Statistical analysis was performed to evaluate CT at each geographic region and observe the relationship between CT and the degree of myopia.

Results: For low myopic eyes, the IOL was measured at 24.619 ± 0.016 mm. The CT (273.85 ± 49.01 µm) was greatest under fovea as is in the case of healthy eyes. Peripheral to the fovea, the mean CT decreased rapidly along the nasal direction, reaching a minimum of 180.65 ± 58.25 µm at 5 mm away from the fovea. There was less of a change in thickness from the fovea in the temporal direction reaching a minimum of 234.25 ± 42.27 µm. In contrast to the low myopic eyes, for moderate and high myopic eyes, CTs were thickest in temporal region (where CT = 194.94 ± 27.28 and 163 ± 34.89 µm, respectively). Like the low myopic eyes, moderate and high myopic eyes had thinnest CTs in the nasal region (where CT = 100.84 ± 16.75 and 86.64 ± 42.6 µm, respectively). High myopic eyes had the longest mean IOL (25.983 ± 0.021 mm), while the IOL of moderate myopia was 25.413 ± 0.022 mm (**p < 0.001). The CT reduction rate was calculated at 31.28 µm/D (diopter) from low to moderate myopia, whilst it is 13.49 µm/D from moderate to high myopia. The similar tendency was found for the IOL reduction rate in our study: 0.265 mm/D from low to moderate myopia, and 0.137 mm/D from moderate to high myopia.

Conclusion: The CT decreases and the IOL increases gradually with the increase of myopic condition. The current results support the theory that choroidal abnormality may play an important role in the pathogenesis of myopic degeneration.

As near-infrared spectroscopy (NIRS) broadens its application area to different age and disease groups, motion artifacts in the NIRS signal due to subject movement is becoming an important challenge. Motion artifacts generally produce signal fluctuations that are larger than physiological NIRS signals, thus it is crucial to correct for them before obtaining an estimate of stimulus evoked hemodynamic responses. There are various methods for correction such as principle component analysis (PCA), wavelet-based filtering and spline interpolation. Here, we introduce a new approach to motion artifact correction, targeted principle component analysis (tPCA), which incorporates a PCA filter only on the segments of data identified as motion artifacts. It is expected that this will overcome the issues of filtering desired signals that plagues standard PCA filtering of entire data sets. We compared the new approach with the most effective motion artifact correction algorithms on a set of data acquired simultaneously with a collodion-fixed probe (low motion artifact content) and a standard Velcro probe (high motion artifact content). Our results show that tPCA gives statistically better results in recovering hemodynamic response function (HRF) as compared to wavelet-based filtering and spline interpolation for the Velcro probe. It results in a significant reduction in mean-squared error (MSE) and significant enhancement in Pearson's correlation coefficient to the true HRF. The collodion-fixed fiber probe with no motion correction performed better than the Velcro probe corrected for motion artifacts in terms of MSE and Pearson's correlation coefficient. Thus, if the experimental study permits, the use of a collodion-fixed fiber probe may be desirable. If the use of a collodion-fixed probe is not feasible, then we suggest the use of tPCA in the processing of motion artifact contaminated data.

NAD⁺/NADH redox state has been implicated in many diseases such as cancer and diabetes as well as in the regulation of embryonic development and aging. To fluorimetrically assess the mitochondrial redox state, Dr. Chance and co-workers measured the fluorescence of NADH and oxidized flavoproteins (Fp) including flavin-adenine-dinucleotide (FAD) and demonstrated their ratio (i.e. the redox ratio) is a sensitive indicator of the mitochondrial redox states. The Chance redox scanner was built to simultaneously measure NADH and Fp in tissue at submillimeter scale in 3D using the freeze-trap protocol. This paper summarizes our recent research experience, development and new applications of the redox scanning technique in collaboration with Dr.Chance beginning in 2005. Dr. Chance initiated or actively involved in many of the projects during the last several years of his life. We advanced the redox scanning technique by measuring the nominal concentrations (in reference to the frozen solution standards) of the endogenous fluorescent analytes, i.e., [NADH] and [Fp] to quantify the redox ratios in various biological tissues. The advancement has enabled us to identify an array of the redox indices as quantitative imaging biomarkers (including [NADH], [Fp], [Fp]/([NADH] + [Fp]), [NADH]/[Fp], and their standard deviations) for studying some important biological questions on cancer and normal tissue metabolism. We found that the redox indices were associated or changed with (1) tumorigenesis (cancer versus non-cancer of human breast tissue biopsies); (2) tumor metastatic potential; (3) tumor glucose uptake; (4) tumor p53 status; (5) PI3K pathway activation in premalignant tissue; (6) therapeutic effects on tumors; (7) embryonic stem cell differentiation; (8) the heart under fasting. Together, our work demonstrated that the tissue redox indices obtained from the redox scanning technique may provide useful information about tissue metabolism and physiology status in normal and diseased tissues. The Chance redox scanner and other redox imaging techniques may have wide-ranging potential applications in many fields, such as cancer, diabetes, developmental process, mitochondrial diseases, neurodegenerative diseases, and aging.

The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD⁺ couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038). No significant change in Fp was found (p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D imaging of the mitochondrial redox state in the heart and provides a useful tool to study heart metabolism and function under normal, dietary-change and pathological conditions at tissue level.

This review summarizes the historical and more recent developments of multiphoton microscopy, as applied to dermatology. Multiphoton microscopy offers several advantages over competing microscopy techniques: there is an inherent axial sectioning, penetration depths that compete well with confocal microscopy on account of the use of near-infrared light, and many two-photon contrast mechanisms, such as second-harmonic generation, have no analogue in one-photon microscopy. While the penetration depths of photons into tissue are typically limited on the order of hundreds of microns, this is of less concern in dermatology, as the skin is thin and readily accessible. As a result, multiphoton microscopy in dermatology has generated a great deal of interest, much of which is summarized here. The review covers the interaction of light and tissue, as well as the various considerations that must be made when designing an instrument. The state of multiphoton microscopy in imaging skin cancer and various other diseases is also discussed, along with the investigation of aging and regeneration phenomena, and finally, the use of multiphoton microscopy to analyze the transdermal transport of drugs, cosmetics and other agents is summarized. The review concludes with a look at potential future research directions, especially those that are necessary to push these techniques into widespread clinical acceptance.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O₂) pups, hyperoxic (90% O₂) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.