Extraction of optical absorption and scattering coefficients from experimental measurements of spatially and/or
spectrally resolved diffuse reflectance typically requires that measurements made on unknown samples be calibrated
using those made on reference phantoms with well characterized optical properties. Here, we derive the optical
scattering and absorption spectra of a solid homogenous resin-phantom using two analytical methods: radially resolved
diffuse reflectance (RRDR) based fitting and spectrally resolved diffuse reflectance (SRDR) based fitting. Radially
resolved data was acquired using a fabricated probe holder which connected one source fiber to 7 detector fibers with
distances ranging between 1.65 to 12.5 mm. Each detector fiber was connected to a spectrometer and spectra ranging
450 to 800 nm were measured when a broadband halogen lamp was used as the source. Diffusion theory based, as well
as scaled Monte Carlo based models were used to fit the spectrally and radially resolved reflectance (on a per
wavelength basis) to derive the absorption and scattering spectra of the solid phantom. To assess the accuracy of these
derived absorption and scattering properties, they were used as reference measurements to reconstruct the optical
properties of liquid phantoms, with well-determined absorption and scattering. Reference optical properties determined
using the SRDR methods were more accurate in reconstructing the optical properties in liquid phantoms. However,
RRDR methods are useful to obtain a spectral profile of the absorption coefficient of an unknown media, for subsequent
analyses using SRDR.
Repair of soft tissue defects of the lips as seen in complex maxillofacial injuries, requires pre-vascularized multi-tissue
composite grafts. Protocols for fabrication of human ex-vivo produced oral mucosal equivalents (EVPOME) composed
of epithelial cells and a dermal equivalent are available to create prelaminated flaps for grafting in patients. However, invivo
assessment of neovascularization of the buried prelaminated flaps remains clinically challenging. Here, we use
diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) to non-invasively quantify
longitudinal changes in the vessel density and blood-flow within EVPOME grafts implanted in the backs of SCID mice
and subsequently to determine the utility of these optical techniques for assessing vascularization of implanted grafts. 20
animals were implanted with EVPOME grafts (1x1x0.05 cm3) in their backs. DRS and DCS measurements were
obtained from each animal both atop the graft site and far away from the graft site, at one week post-implantation, each
week, for four consecutive weeks. DRS spectra were analyzed using an inverse Monte Carlo model to extract tissue
absorption and scattering coefficients, which were then used to extract blood flow information by fitting the
experimental DCS traces. There were clear differences in the mean optical parameters (averaged across all mice) at the
graft site vs. the off-site measurements. Both the total hemoglobin concentration (from DRS) and the relative blood flow
(from DCS) peaked at week 3 at the graft site and declined to the off-site values by week 4. The optical parameters
remained relatively constant throughout 4 weeks for the off-site measurements.
There is a critical unmet clinical need for a device that can monitor and predict the onset of shock: hemorrhagic shock or bleeding to death, septic shock or systemic infection, and cardiogenic shock or blood flow and tissue oxygenation impairment due to heart attack. Together these represent 141 M patients per year. We have developed a monitor for shock based on measuring blood flow in peripheral (skin) capillary beds using diffuse correlation spectroscopy, a form of dynamic light scattering, and have demonstrated proof-of-principle both in pigs and humans. Our results show that skin blood flow measurement, either alone or in conjunction with other hemodynamic properties such as heart rate variability, pulse pressure variability, and tissue oxygenation, can meet this unmet need in a small self-contained patch-like device in conjunction with a hand-held processing unit. In this paper we describe and discuss the experimental work and the multivariate statistical analysis performed to demonstrate proof-of-principle of the concept.
Photodynamic therapy (PDT) is becoming a treatment of choice for cancer because of
its low cost, high effectiveness and low damage to healthy tissue. Successful PDT outcome
depends on accurate dosimetry, which is currently lacking, leading to variable and/or
ineffective treatment outcome. We report on our research and developmental efforts
towards an implicit dosimetric method for PDT that will provide an accurate assessment of
treatment effectiveness by continuous monitoring of the in vivo drug concentration and the
oxygen concentration in tissue. This approach uses the same tools presently available for
PDT, making it attractive to the health professionals without increasing treatment cost.
Accident victims and victims of explosive devices often suffer from complex maxillofacial
injuries. The lips are one of the most difficult areas of the face to reconstruct after an avulsion.
Lip avulsion results in compromised facial esthetics and functions of speech and mastication.
The process of reconstruction requires assessment of the vascularization of grafted ex vivo
engineered tissue while it is buried underneath the skin. We describe the design and animal
testing of a hand-held surgical probe based upon diffuse correlation spectroscopy to assess
vascularization.
We have developed the necessary theoretical
framework and the basic instrumental design parameters to
enable mapping of subsurface blood dynamics and tissue
oxygenation for patients undergoing skin graft procedures.
This analysis forms the basis for developing a simple patch
geometry, which can be used to map by diffuse optical
techniques blood flow velocity and tissue oxygenation as a
function of depth in subsurface tissue.skin graft, diffuse
correlation analysis, oxygen saturation.
We present the design principles and performance characteristics of a prototype user-friendly shear force
based Tip-Enhanced Raman Spectroscopy system. High numerical aperture reflective optics are utilized to
optimize photon delivery and collection, while allowing for interrogation of samples with varying
resistivities, thicknesses, and opacities. The integration of tips and tuning forks into manufacturable units is
investigated to facilitate simple tip replacement. Finally we discuss methods to mitigate the remaining
challenges to the technique becoming routine and user-friendly.
In this work, we present research performed towards the realization of a hypoxia monitor that can detect the onset of
hypoxia within a minute with very low false positive and false negative rates. We report the development of the next-generation
hypoxia monitor with the capability to simultaneously detect various physiological parameters that change in
response to reduced oxygen availability and identify the onset of hypoxia based on the changes in their cross-correlation
signals. Significant improvements are obtained over the conventional techniques that are used currently to measure
some of the physiological parameters including blood oxygen saturation and blood flow velocity. We demonstrate that a
simple patch geometry holding three LEDs and two single photon sensitive detectors can be used to simultaneously
obtain the heart rate, respiratory rate, blood flow velocity and blood oxygen saturation levels and in less than one minute
analyze their cross-correlation signals to identify the onset of hypoxia from the more benign auto-regulatory response to
stress.
We provide a detailed signal-to-noise analysis for 3D imaging of luminescence from a biomarker to detect hypoxic
tumors in deep tissue. Preliminary studies on phantom tissues with inclusions and having homogeneous scattering and
absorption coefficient of μs' ~ 15-20 cm-1 and μa ~ 2 cm-1 respectively, are reported as a function of oxygen tension,
luminophore concentration, and tissue depth. The technique's sensitivity in terms of determination of spatial resolution is
discussed.
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