Atherosclerosis is the most common underlying cause of vascular disease, occurring in multiple arterial beds
including the carotid, coronary, and femoral arteries. Atherosclerosis is an inflammatory process occurring in arterial
tissue, involving the subintimal accumulation of low-density lipoproteins (LDL). Little is known about the rates at
which these accumulations occur. Measurements of the permeability rate of LDL, and other lipoproteins such as
high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL), could help gain a better understanding of
the mechanisms involved in the development of atherosclerotic lesions. The permeation of VLDL, LDL, HDL, and
glucose was monitored and quantified in normal and diseased human carotid endarterectomy tissues at 20°C and
37°C using optical coherence tomography (OCT). The rates for LDL permeation through normal tissue at 20°C was
(3.16 ± 0.37) × 10-5 cm/sec and at 37°C was (4.77 ± 0.48) × 10-5 cm/sec, significantly greater (p<0.05) than the rates
for diseased tissue at these temperatures ((1.97 ± 0.34) × 10-5 cm/sec and (2.01 ± 0.23) ×
10-5 cm/sec, respectively).
The observed results support previous suggestions of an enhanced transport mechanism specific to LDL. This study
effectively uses optical coherence tomography to measure the rates of permeation of vascular tissue by the range of
naturally occurring lipoproteins.
In imaging of turbid biological samples using optical techniques, optical clearing methods can compensate for the lack of
light penetration due to strong attenuation. The addition of optical clearing agents into scattering media increases the
optical homogeneity of the sample and reduces its turbidity, allowing for the increased light penetration. In this study we
investigated the extent of optical clearing in porcine skin by utilizing various concentrations of glucose solution. A goldplated
mirror was fixed beneath the tissue and percentage clearing was determined by measuring the change in intensity
of optical coherence tomography light returning from the mirror over time. A ratio of percentage clearing per tissue
thickness for 10%, 30%, and 50% glucose was determined to be to be (4.7 ± 1.6%) mm-1 (n = 6), (10.6 ± 2.0%) mm-1 (n
= 7), and (21.8 ± 2.2%) mm-1 (n = 5), respectively. Although the extent of optical clearing in porcine skin was more
significant for 50% glucose, the osmotic stress on the sample can cause considerable morphology change, thus a suitable
concentration must be chosen for particular circumstances.
Preservation of porcine aortic tissue at 4°C in phosphate buffered saline (PBS) was monitored for a period of 10
days. Optical coherence tomography (OCT) was used to indirectly quantify the permeation of glucose, with the objective
of assessing the structural integrity of the tissue. The average permeability rate for the first day was calculated to be (2.32
± 0.46) × 10-5 cm/s. After 10 days of storage the average permeability rate was found to be (7.37 ± 0.41) × 10-5 cm/s --
nearly a 200% increase. A z-test performed on the permeability rate results verified that after 4 days of storage the
permeability rate had significantly changed (p<0.05). Histology was used to validate the OCT results by quantifying
changes in pore area. An increase in pore size paralleled the increase in permeability rate over the 10 day storage period.
A parallel experiment demonstrated that increasing pore size was not accompanied by release of protein from the tissue
over the storage period. The results suggest that tissues can maintain their structural stability for at least three days at 4°C
in PBS.
Cardiovascular disease is among the leading causes of death in the United States. Specifically, atherosclerosis is an increasingly devastating contributor to the tally and has been found to be a byproduct of arterial permeability irregularities in regards to lipoprotein penetration. To further explore arterial physiology and molecular transport, the imaging technique of Optical Coherence Tomography (OCT) was employed. With OCT, the permeation of glucose
(MW = 180 Da), low density lipoprotein (LDL; MW = 2.1 × 106 Da), and high density lipoprotein (HDL; MW = 2.5 ×
105 Da) in human carotid tissue was studied to determine the effect of different molecular characteristics on permeation
in atherosclerotic tissues. The permeability rates calculated from the diffusion of the molecular agents into the abnormal
carotid tissue samples is compared to those of normal, healthy tissue. The results show that in the abnormal tissue, the
permeation of agents correlate to the size constraints. The larger molecules of LDL diffuse the slowest, while the
smallest molecules of glucose diffuse the fastest. However, in normal tissue, LDL permeates at a faster rate than the
other two agents, implying the existence of a transport mechanism that facilitates the passage of LDL molecules. These
results highlight the capability of OCT as a sensitive and specific imaging technique as well as provide significant
information to the understanding of atherosclerosis and its effect on tissue properties.
Monitoring and quantifying the permeability of different drugs and chemical solutions through ocular tissues is of great
importance due to its potential use in pharmacological research. In this study, Optical Coherence Tomography, a
relatively new innovation in biomedical imaging was used for the functional imaging of glucose diffusion in the sclera of
the eye. The permeability coefficient for different glucose concentrations was quantified non-destructively in order to
compare the effect of glucose concentration on its rate of diffusion. In these in vitro experiments, fresh New Zealand
white rabbit eyes were imaged during the diffusion of different glucose concentrations (10, 15, 20, and 25%). The
nonlinearity of the permeability coefficient in the tissue with differing glucose concentrations was evident. The results
suggest an inversely proportional relationship between the permeability coefficient and the glucose concentration in
epithelial tissues. The permeability coefficient of glucose declined from (1.67 ± 0.17) × 10-5 cm/sec to (5.08 ± 0.23) × 10-6 cm/sec for the 10% and 25% glucose solutions, respectively. Furthermore, the nonlinear relationship between the
permeability rate and the concentration of hyperosmotic solutions demonstrated in this study could be further utilized in
numerous scientific and clinical fields such as optical clearing of tissues and noninvasive diagnosis of eye diseases.
The cornea contributes about 65% of the eye's ability to refract light. Thus, any fluctuation in corneal thickness can
cause noticeable changes in vision. The presence of glucose molecules induces a driving force for water to leave the
collagen fibrils in the cornea due to the concentration gradient created, thus changing its thickness. In this study, the
effect of various milli-molar glucose concentrations on corneal thickness was explored using Optical Coherence
Tomography. Whole rabbit eyes were placed in a specially designed dish while immersed in saline to ensure proper
hydration of the eye. The cornea was imaged for 10 minutes. In 30 minute increments, a higher concentration of
glucose was added, bringing the overall glucose concentration to 10, 15, 20, 25, and 30 mM. The thickness of the
cornea was measured every 2 minutes. Ultimately, an inverse relationship was observed, indicating that the increase
in glucose concentration yielded a decrease in the corneal thickness. From three separate experiments, the cornea
experienced 8 ± 1, 27 ± 1, 44 ± 3, 58 ± 3, and 64 ± 3 μm decrease in thickness from its starting value while exposed
to 10, 15, 20, 25, and 30 mM solutions of glucose, respectively. This relationship provides insight on the
physiological changes of the cornea as a result of different glucose concentrations. This could potentially be useful
in monitoring blood-glucose levels through the eye.
Aside from other ocular drug delivery methods, topical application and follow up drug diffusion through
the cornea and sclera of the eye remain the favored method, as they impose the least pain and discomfort to the
patient. However, this delivery route suffers from the low permeability of epithelial tissues and drug washout, thus
reducing the effectiveness of the drug and ability to reach its target in effective concentrations. In order to better
understand the behavioral characteristics of diffusion in ocular tissue, a method for noninvasive imaging of drug
diffusion is needed. Due to its high resolution and depth-resolved imaging capabilities, optical coherence
tomography (OCT) has been utilized in quantifying the molecular transport of different drugs and analytes in vitro in
the sclera and the cornea. Diffusion of Metronidazole (0.5%), Dexamethasone (0.2%), Ciprofloxacin (0.3%),
Mannitol (20%), and glucose solution (20%) in rabbit sclera and cornea were examined. Their permeability
coefficients were calculated by using OCT signal slope and depth-resolved amplitude methods as function of time
and tissue depth. For instance, mannitol was found to have a permeability coefficient of (8.99 ± 1.43) × 10-6 cm/s in
cornea (n=4) and (6.18 ± 1.08) × 10-6 cm/s in sclera (n=5). We also demonstrate the capability of OCT technique for
depth-resolved monitoring and quantifying of glucose diffusion in different layers of the sclera. We found that the
glucose diffusion rate is not uniform throughout the tissue and is increased from approximately (2.39 ± 0.73) × 10-6
cm/s at the epithelial side to (8.63 ± 0.27) × 10-6 cm/s close to the endothelial side of the sclera. In addition,
discrepancy in the permeability rates of glucose solutions with different concentrations was observed. Such diffusion
studies could enhance our knowledge and potentially pave the way for advancements of therapeutic and diagnostic
techniques in the treatment of ocular diseases.
Studying hemodynamic changes during early mammalian embryonic development is critical for further advances in prevention, diagnostics, and treatment of congenital cardiovascular (CV) birth defects and diseases. Doppler optical coherence tomography (OCT) has been shown to provide sensitive measurements of blood flow in avian and amphibian embryos. We combined Doppler swept-source optical coherence tomography (DSS-OCT) and live mouse embryo culture to analyze blood flow dynamics in early embryos. SS-OCT structural imaging was used for the reconstruction of embryo morphology and the orientation of blood vessels, which is required for calculating flow velocity from the Doppler measurements. Spatially and temporally resolved blood flow profiles are presented for the dorsal aorta and a yolk sac vessel in a 9.5-day embryo. We demonstrate that DSS-OCT can be successfully used for structural analysis and spatially and temporally resolved hemodynamic measurements in developing early mammalian embryos.
The calculation of permeability coefficient of analytes could potentially be used in a variety of basic science and
clinical fields, as well as advanced diagnostic imaging. Before this can occur, a more thorough understanding of the
diffusion rate of analytes in biological tissues is needed. For this task, we utilized Optical Coherence Tomography for
the functional imaging of glucose diffusion through rabbit sclera tissues. The permeability coefficients were calculated
for different concentrations of glucose solution as they diffused through the tissue. From the experiments performed it
was noticed that the concentration of the analyte was inversely proportional to the permeability coefficient calculated.
The permeability coefficient of glucose solution with lower concentration was faster when compared with higher
concentration. The decrease in the permeability coefficient ranged from (1.67 ± 0.17) x 10-5 cm/sec with the 10%
glucose solution to (5.08 ± 0.23) x 10-6cm/sec of 25% glucose solution. The results of this study could expand the use
of the permeability coefficient into the field of diagnostic imaging.
High in-depth resolution imaging, such as Optical Coherence Tomography, could be the next frontier in noninvasive quantification of diffusion in epithelial tissues. In this study we employed OCT in a method that could help differentiate various forms of atherosclerosis and distinguish between normal and diseased tissue. The diffusion of glucose solution in normal and diseased pig aorta in vitro was monitored and the permeability coefficient was calculated. The results suggest that this OCT method may have high potential for early detection of tissue abnormalities while used in diffusion studies.
Imaging of biological tissues with optical coherence tomography (OCT) poses a great interest for its capability to noninvasively outline subsurface microstructures within tissues. However, a major limitation for many optical imaging techniques is inadequate depth penetration of light in turbid media, which is bounded to just a few millimeters. There have been several attempts to improve light penetration depth in biological tissues, including application of different tissue optical clearing methods. In this study, an aqueous solution of glucose (40%) is added to rabbit sclera in vitro, where depth-resolved permeability coefficients and optical clearing are calculated with OCT. The permeability rate in regions in the upper 80- to 100-µm region is found to be different from that of regions in the deeper 100-µm region: (6.01±0.37)×10−6 cm/sec and (2.84±0.68)×10−5 cm/sec, respectively. A difference in percent clearing is also noted. Optical clearing of the upper region is about 10% and increased to 17 to 22% in the one beneath. These results demonstrate the capability of OCT-based methods to not only measure the diffusion rate and optical clearing of a tissue, but also its ability of functional differentiation between layers of epithelial tissues.
Noninvasive assessments of optical clearing and permeability coefficients of tissues pose great possibilities in
advanced diagnostics and medical applications. In order for both of these to become utilized in common practice, a
greater understanding of molecular diffusivity in multi-layered tissues is required. In biological tissues, the different
layers are comprised of differentiated cells and/or collagen fibrils which come together to form that specific layer.
Therefore, a patchwork of layers is created each with its own set of properties. In our current study we analyze and
describe the dynamics of matter diffusion and its underlying non-linear character in various epithelial tissues. For
instance, the permeability coefficient (PC) of 20% concentrated mannitol in the rabbit eye sclera showed an
increasing trend as it was measured deeper into the tissue. The PC was found to be 2.18 × 10-6 cm/sec at 50 μm
away from the epithelial layer. It increased to about 7.33 × 10-6 cm/sec when it was computed at 210 μm from the
epithelial layer. Different layers in the sclera showed different clearing response to glucose solution as well. The
first 100 μm region from the epithelial layer cleared about 10% whereas the next 100 μm cleared about 17-22%.
The importance of this study is that it may offer a novel explanation to how a layer's composition affects optical
clearing and the permeability coefficient of analytes and solutions.
Noninvasive cardiovascular imaging could lead to the early detection and timely treatment of complex atherosclerotic lesions responsible for major cardiovascular events. Recent investigations have suggested that optical coherence tomography (OCT) is an ideal diagnostic tool due to the high resolution this technology achieves in discriminating the different features of atherosclerotic lesions based on structural imaging. We explore the capability of OCT for functional imaging of normal and atherosclerotic aortic tissues based on time- and depth-resolved quantification of the permeability of biomolecules through these tissues. The permeability coefficient of 20% aqueous solution of glucose was found to be (6.80±0.18)×10−6 cm/s in normal aortas and (2.69±0.42)×10−5 cm/s in aortas with atherosclerotic disease. The results suggest that this new OCT functional imaging method—the assessment of the permeability coefficients of various physiologically neutral biomolecules in vascular tissues—could assist in early diagnosing and detecting the different components of atherosclerotic lesions.
Optical coherence tomography (OCT) is a noninvasive imaging technique with high in-depth resolution. We employed OCT technique for monitoring and quantification of analyte and drug diffusion in cornea and sclera of rabbit eyes in vitro. Different analytes and drugs such as metronidazole, dexamethasone, ciprofloxacin, mannitol, and glucose solution were studied and whose permeability coefficients were calculated. Drug diffusion monitoring was performed as a function of time and as a function of depth. Obtained results suggest that OCT technique might be used for analyte diffusion studies in connective and epithelial tissues.
There is increasing interest in determining drug diffusion rates in ocular tissues. In this paper we present results of our pilot
investigation of depth-resolved monitoring of water diffusion in rabbit cornea using Optical Coherence Tomography (OCT)
technique. We monitored changes in the local scattering coefficient of rabbit cornea in vitro as water propagated inside the
tissue. Tissue hydration and saturation phases were clearly seen. The water diffusion rate was about 1.48-5cm/sec. The experimental results suggest that water diffusion rate in cornea can be potentially measured with the OCT system noninvasively with high precision and accuracy.
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