Functional near-infrared spectroscopy (fNIRS) is a well-known technique for non-invasively measuring cerebral blood oxygenation, and many studies have demonstrated that fNIRS signals can be related to cognitive function. However, the fNIRS signal is attenuated by the skin, while scalp blood content has been reported to influence cerebral oxygenation measurements. Mechanical indentation has been shown to increase light transmission through soft tissues by causing interstitial water and blood flow away from the compressed region. To study the effects of indentation on fNIRS, a commercial fNIRS system with 16 emitter/detector pairs was used to measure cerebral blood oxygenation at 2 Hz. This device used diffuse reflectance at 730 nm and 850 nm to calculate deoxy- and oxy-hemoglobin concentrations. A borosilicate glass hemisphere was epoxied over each sensor to function as both an indenter and a lens. After placing the indenter/sensor assembly on the forehead, a pair of plastic bands was placed on top of the fNIRS headband and strapped to the head to provide uniform pressure and tightened to approx. 15 N per strap. Cerebral blood oxygenation was recorded during a breath holding regime (15 second hold, 15 second rest, 6 cycles) in 4 human subjects both with and without the indenter array. Results showed that indentation increased raw signal intensity by 85 ± 35%, and that indentation increased amplitude of hemoglobin changes during breath cycles by 313% ± 105%. These results suggest that indentation improves sensing of cerebral blood oxygenation, and may potentially enable sensing of deeper brain tissues.
This paper describes a new infusion catheter, based on our fiberoptic microneedle device (FMD), designed with the objective of photothermally augmenting the volumetric dispersal of infused therapeutics. We hypothesize that concurrent delivery of laser energy, causing mild localized photothermal heating (4-5 °C), will increase the spatial dispersal of infused chemotherapy over a long infusion period. Agarose brain phantoms, which mimic the brain’s mechanical and fluid conduction properties, were constructed from 0.6 wt% Agarose in aqueous solution. FMDs were fabricated by adhering a multimode fiberoptic to a silica capillary tube, such that their flat-polished tips co-terminated. Continuous wave 1064 nm light was delivered simultaneously with FD&C Blue #2 (5%) dye into phantoms. Preliminary experiments, where co-delivery was tested against fluid delivery alone (through symmetrical infusions into in vivo rodent models), were also conducted. In the Agarose phantoms, volumetric dispersal was demonstrated to increase by more than 3-fold over a four-hour infusion time frame for co-delivery relative to infusion-only controls. Both forward and backward (reflux) infusions were also observed to increase slightly. Increased volumetric dispersal was demonstrated with co-delivery in an in vivo rodent model. Photothermal augmentation of infusion was demonstrated to influence the directionality and increase the volume of dye dispersal in Agarose brain phantoms. With further development, FMDs may enable a greater distribution of chemotherapeutic agents during CED therapy of brain tumors.
A scanning-fiber-based method developed for imaging bioengineered tissue constructs such as synthetic carotid arteries is reported. Our approach is based on directly embedding one or more hollow-core silica fibers within the tissue scaffold to function as micro-imaging channels (MIC). The imaging process is carried out by translating and rotating an angle-polished fiber micro-mirror within the MIC to scan excitation light across the tissue scaffold. The locally emitted fluorescent signals are captured using an electron multiplying CCD camera and then mapped into fluorophore distributions according to fiber micro-mirror positions. Using an optical phantom composed of fluorescent microspheres, tissue scaffolds, and porcine skin, we demonstrated single-cell-level imaging resolution (20 to 30 μm) at an imaging depth that exceeds the photon transport mean free path by one order of magnitude. This result suggests that the imaging depth is no longer constrained by photon scattering, but rather by the requirement that the fluorophore signal overcomes the background “noise” generated by processes such as scaffold autofluorescence. Finally, we demonstrated the compatibility of our imaging method with tissue engineering by visualizing endothelial cells labeled with green fluorescent protein through a ∼500 μm thick and highly scattering electrospun scaffold.
The degree by which optical properties of tumors are altered following introduction of carbon nanotubes (CNTs) of varying concentration and type is poorly understood, making it difficult to predict the impact of CNT inclusion on the photothermal response to laser therapies. Optical properties were measured of phantoms representative of breast tumor tissue incorporated with multiwalled carbon nanotubes (MWNTs), single-walled carbon nanotubes (SWNTs), and single-walled carbon nanohorns (SWNHs) of varying concentration (0.01-0.1 mg/ml). Tissue phantoms were made from sodium alginate (3 g/ml) incorporated with polystyrene microbeads (3 μm diam and 1 mg/ml) and talc-France powder (40 mg/ml). Absorption (μa) and reduced scattering (μs′) coefficients of phantoms containing CNTs were determined by the inverse adding-doubling algorithm for the wavelength range of 400-1300 nm. Optical properties of phantoms without CNTs were in the range of μa = 1.04-0.06 mm−1 and μs′ = 0.05-0.07 mm−1 at a wavelength of 900 nm, which corresponds with published data for human breast tumor tissue. Incorporating MWNTs, SWNTs, and SWNHs in phantoms with a concentration of 0.1 mg/ml increased (μa) by 20- to 30-fold, 5- to 6-fold, and 9- to 14-fold, respectively, for the wavelength range of 800-1100 nm with minimal change in μs′ (1.2- to 1.3-fold). Introduction of CNTs into tissue phantoms increased absorption, providing a means to enhance photothermal therapy.
We report results of a study to evaluate effectiveness of a mechanical tissue optical clearing device (TOCD) using optical coherence tomography (OCT). The TOCD uses a pin array and vacuum pressure source to compress localized regions of the skin surface. OCT images (850 and 1310 nm) of in vivo human skin indicate application of the TOCD provides an up to threefold increased light penetration depth at spatial positions correlated with pin indentations. Increased contrast of the epidermal-dermal junction in OCT images spatially correlates with indented zones. OCT M-scans recorded while applying the TOCD indicate optical penetration depth monotonically increased, with most improvement at early times (5 to 10 s) of TOCD vacuum application. OCT M-scans of ex vivo porcine skin compressed using the TOCD suggest average group refractive index of the tissue increased, corresponding to a decrease in water concentration. Results of our study indicate that mechanical optical clearing of skin may provide an effective and efficient means to deliver increased light fluence to dermal and subdermal regions.
We report results of a study to evaluate effectiveness of a mechanical tissue optical
clearing device (TOCD) using optical coherence tomography (OCT). The TOCD consists
of a pin array and vacuum pressure source applied directly to the skin surface. OCT
images (850 and 1310 nm) of in vivo human skin indicate an increased light penetration
depth (enhanced approximately 2 fold over peripheral tissue) which spatially correlates with
TOCD pin indentations. Increased contrast of the epidermal-dermal junction in OCT
images spatially correlates with indented zones. OCT M-scans (time sequence of depth
scans) indicate optical penetration depth monotonically increased throughout the entire
image acquisition period with most improvement at early times of TOCD application with
vacuum. Results of our study suggest that mechanical optical clearing of skin may provide
a means to deliver increased light fluence to dermal and subdermal regions.
Previous studies identified various mechanisms of light scattering reduction in tissue induced by chemical agents. Our results suggest that dehydration is an important mechanism of optical clearing in collagenous and cellular tissue. Photographic and optical coherence tomography images indicate that air-immersed skin and tendon specimens become similarly transparent to glycerol-immersed specimens. Transmission electron microscopy images reveal that dehydration causes individual scattering particles such as collagen fibrils and organelles to become more densely packed, but does not significantly alter size. A heuristic particle-interaction model predicts that the scattering particle volume fraction increase can contribute substantially to optical clearing in collagenous and cellular tissue.
The mechanisms of optical clearing in cellular tissue in response to application of a hyperosmotic solute were theoretically considered using the Rayleigh-Gans approximation to scattering. The effect on scattering coefficient due to changes of three input parameters including refractive index ratio, scatterer size, and scatterer volume fraction were investigated. Decreasing refractive index ratio has the greatest effect on decreasing tissue scattering coefficient, and this parameter is likely to undergo a large variation. Decreasing scatterer size can result in a slight increase or decrease in tissue scattering coefficient depending on initial scatterer size, percent decrease in radius, and wavelength. The effect of tissue scattering coefficient due to an increase in the volume fraction of scatterers depends on initial scatterer volume fraction and percent change. Scattering always decreases when initial scatterer volume fraction is greater than .5. Results of simulations illustrate the high sensitivity of changes in tissue scattering due to the initial and final states of these parameters. Improved understanding of the mechanisms of tissue clearing will require accurate experimental measurement of these input parameters.
We describe a methodology to record spatial variation of refractive index of porcine renal artery using differential phase optical coherence tomography (DP-OCT). DP-OCT provides a quantitative measure of thin specimen phase retardation and refractive index with phase resolution of 5 nm and lateral resolution of 3 mm. DP-OCT instrumentation is an all-fiber, dual channel Michelson interferometer constructed using polarization maintaining fiber. Two orthogonal polarization modes of light are spatially separated using a Wollaston prism and directed into separate photoreceivers. Because phase noise in the environment is equally present in both channels, computation of phase difference between the two signal channels is attributed exclusively to variation in the specimen's composite refractive index. Porcine renal artery is freshly harvested from a local slaughter house. The lumen is cut open and sliced at 5 mm thickness. Microscopic slide for the tissue section is processed by standard histology method with mounting media. Two dimensional en face dual-channel phase images are taken over 150 mm x 200 mm region on the microscopic slide and the images are reconstructed by plotting relative phase variation as the OCT beam is moved across the artery cross section.
Our recent research has shown that skin becomes temporarily transparent when a hyper-osmotic agent such as glycerol is introduced into the tissue. Local dehydration and index matching reduce light scattering which increases the penetration depth of collimated light. We have shown that when glycerol is applied to in vivo hamster skin, the resulting transparency is sufficient to allow visualization of blood vessels, and there is a temporary reduction in local blood flow. The reduced blood flow combined with greater light delivery significantly reduces the laser fluence rate [W/cm2] required to coagulate dermal blood vessels.
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