Steven Golowich, Ronald Lockwood, Richard Nadile, Stuart Biggar, Marius Albota, Rajan Gurjar, Lin Stowe, Luke Skelly, Ian Fletcher, Ping Fung, Sarah Klein, John Jacobson, Charles Gulley
The problem of spectral reflectance retrieval of surfaces via remote hyperspectral imaging is challenging even in benign scenarios, and becomes dramatically more difficult under complex illumination conditions. Shadows, reflections from nearby structures, and atmospheric scattering can all severely impact the observed radiance from ground-level surfaces. In order to study this problem, MIT Lincoln Laboratory recently conducted an airborne data collection experiment that included hyperspectral, laser radar, and pan-chromatic modalities. A comprehensive ground truth data set and extensive efforts directed at sensor characterization makes this data set ideal for the development of hyperspectral exploitation algorithms.
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 paper we present the details of a Diffuse Optical Tomographic (DOT) prototype instrument developed and
characterized at RMD for concurrent operation with Magnetic Resonance Imaging (MRI) to obtain high resolution
spatial and functional images of hypoxic tumor tissue. We have developed a new system designed for in-vivo imaging
of luminescent agents that respond to tissue oxygenation to improve the contrast and spatial resolution of functional
optical images in deep tissue. High-resolution spatial and anatomical information obtained from MRI images is used to
improve the accuracy of the reconstructed optical images. The time domain lifetime imaging module has parallel
acquisition across a cooled 16-element avalanche photodiode (APD) array for high resolution and high throughput
imaging. The low-cost, compact lifetime imager is compatible with high magnetic and RF fields associated with MR
units in hybrid imaging systems. Using this APD module in a dual-modality imaging setup, phantom imaging was
performed to obtain oxygenation images with high resolution and contrast. Optical image reconstruction is aided by
spatial guidance obtained from the actual phantom dimensions to improve the accuracy of these images.
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.
KEYWORDS: Modulation, Avalanche photodetectors, Signal to noise ratio, Receivers, Heterodyning, Amplifiers, Signal detection, Photodetectors, Signal attenuation, Sensors
In this work, we present research performed to improve the receiver characteristics for underwater imaging applications
using the hybrid lidar-radar detection technique. We report the development of the next-generation coherent heterodyne
receiver using modulation of the optical receiver's amplifier gain. Significant advantages in the receiver specifications
are achieved using a large-area, high gain, low-noise silicon avalanche photodiode (APD) as the photodetector cum
frequency mixer-demodulator. We demonstrate that heterodyne detection by gain modulation of APD can be used to
increase the signal-to-noise ratio, detection sensitivity and bandwidth for the hybrid receiver system.
Geiger-mode photodiodes (GPD) act as binary photon detectors that convert analog light intensity into digital pulses.
Fabrication of arrays of GPD in a CMOS environment simplifies the integration of signal-processing electronics to
enhance the performance and provide a low-cost detector-on-a-chip platform. Such an instrument facilitates imaging
applications with extremely low light and confined volumes. High sensitivity reading of small samples enables twodimensional
imaging of DNA arrays and for tracking single molecules, and observing their dynamic behavior. In this
work, we describe the performance of a prototype imaging detector of GPD pixels, with integrated active quenching for
use in imaging of 2D objects using fluorescent labels. We demonstrate the integration of on-chip memory and a parallel
readout interface for an array of CMOS GPD pixels as progress toward an all-digital detector on a chip. We also
describe advances in pixel-level signal processing and solid-state photomultiplier developments.
In this work, we present research in using confocal optical techniques with femtolitre focal volumes and obtain very high
signal-to-noise and signal-to-background ratios for single molecule detection (SMD). We were able to achieve
improved signal strength by using highly fluorescent quantum dots and nanopatterned substrates to obtain plasmon
induced resonant fluorescence enhancement. A method to simultaneously using multiple excitation spots without the
use of confocal apertures and an array of single photon sensitive Geiger mode avalanche photodiodes was used to
increase the throughput of the detection system. Using this highly sensitive SMD system, we detect small quantities of
synthetic DNA through hybridization eliminating the need of polymerase chain reaction.
Light scattering spectroscopy (LSS) is a promising optical technique developed for quantitative characterization of tissue morphology as well as in vivo detection and diagnosis of disease such as early cancer. LSS employs a wavelength dependent component of light scattered by epithelial cells and other tissues to obtain information about subcellular structure. We present two novel modalities of LSS, LSS imaging and scattering angle sensitive LSS (a/LSS). LSS imaging provides quantitative information about the epithelial cell nuclei, such as nuclear size, degree of pleomorphism, hyperchromasia, and amount of chromatin. It allows mapping these histological properties over wide areas of epithelial lining. We show that LSS imaging can be used to detect precancerous lesions in optically accessible organs. Using a/LSS, which enables characterization of tissue components with sizes smaller than the wavelength of light, we show that the number of subcellular components with the sizes between 30 nm and few microns scales with the size according to an inverse power-law. We show that the size distribution exponent is an important parameter characterizing tissue organization, for example the balance between stochasticity and order, and has a potential to be applicable for early cancer diagnosis and characterization.
We presented two approaches for separating a diffusive component of the backscattered signal originated in deep tissue layers and a non-diffusive single backscattering component which backscattered from a thin epithelial layer. Both approaches can be effective and have their advantages and disadvantages. The modeling technique can provide important information about hemoglobin concentration, oxygenation, and average scattering properties of the mucosal tissue. On the other hand, when applied to new tissues, it has to be adjusted to take into account tissue morphology. Also, the polarization technique can be very robust and more effective in background removal. However, it lacks extracting capabilities of the modeling technique. Both techniques can be quite valuable and compliment each other in a future clinical device.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.