In this work, we demonstrate the ability to image and quantify airway changes, we were able to quantify a decrease in airway compliance. The proposed approach will enable further investigations of using OCT assessing pulmonary injury to prevent/treat ARDS using a chlorine inhalation injury model, as well as diagnosing of large airway injury and compliance change due to airway toxic chemical exposure. With enhanced portability over conventional bronchoscopy, we believe our system is capable of field hospital deployment and investigating airway conditions in warfighters. Combining OCT and pressure transducer with bronchoscopy would enhance assessment and treatment of large airway chemical injury.
In this work, we demonstrate the ability to image and quantify airway changes, edema, and epithelial layer separation using OCT and automated tissue boundary identification in the rabbit large airways as early as 30-minutes post-chlorine gas exposure. We propose this novel approach will enable further investigations into using OCT for pre-hospital and point-of-care diagnostics of large airway injury due to airway toxic chemical exposure. With enhanced portability over conventional bronchoscopy, we believe our system is capable of field hospital deployment and investigating airway conditions in warfighters. Combining OCT with bronchoscopy would enhance the assessment and treatment of large airway chemical injury.
Spectrally encoded interferometric microscopy (SEIM) is capable of detecting nanometer displacement at a frame rate in the kilohertz regime. By employing a wavelength-sweeping laser and a spectral disperser, SEIM can achieve en face imaging via one-axis scanning. In this study, we compared different processing algorithms for visualizing cilia-induced motion. Our Doppler-based method, combined with phase stabilization and bulk motion correction, provides the highest sensitivity for measuring ciliary beating frequency amongst the tested methods. Traveling waves induced by coordinated cilia motion were visualized. These results demonstrate the potential clinical utility of SEIM for monitoring respiratory function and therapeutic effects.
A major need exists for methods to assess organ oxidative metabolic states in vivo. By contrasting the responses to cyanide (CN) poisoning versus hemorrhage in animal models, we demonstrate that diffuse optical spectroscopy (DOS) can detect cytochrome c oxidase (CcO) redox states. Intermittent decreases in inspired O2 from 100% to 21% were applied before, during, and after CN poisoning, hemorrhage, and resuscitation in rabbits. Continuous DOS measurements of total hemoglobin, oxyhemoglobin, deoxyhemoglobin, and oxidized and reduced CcO from muscle were obtained. Rabbit hemorrhage was accomplished with stepwise removal of blood, followed by blood resuscitation. CN treated rabbits received 0.166 mg/min NaCN infusion. During hemorrhage, CcO redox state became reduced concurrently with decreases in oxyhemoglobin, resulting from reduced tissue oxygen delivery and hypoxia. In contrast, during CN infusion, CcO redox state decreased while oxyhemoglobin concentration increased due to CN binding and reduction of CcO with resultant inhibition of the electron transport chain. Spectral absorption similarities between hemoglobin and CcO make noninvasive spectroscopic distinction of CcO redox states difficult. By contrasting physiological perturbations of CN poisoning versus hemorrhage, we demonstrate that DOS measured CcO redox state changes are decoupled from hemoglobin concentration measurement changes.
Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.
Matthew Brenner, Sari Mahon, Jangwoen Lee, Jae Gwan Kim, David Mukai, Seth Goodman, Kelly Kreuter, Rebecca Ahdout, Othman Mohammad, Vijay Sharma, William Blackledge, Gerry Boss
Our purpose is to compare cobinamide to hydroxocobalamin in reversing cyanide (CN)-induced physiologic effects in an animal model using diffuse optical spectroscopy (DOS). Cyanide poisoning is a major threat worldwide. Cobinamide is a novel molecule that can bind two molecules of cyanide, has a much higher binding affinity than hydroxocobalamin, and is more water soluble. We investigated the ability of equimolar doses of cobinamide and hydroxocobalamin to reverse the effects of cyanide exposure in an animal model monitored continuously by DOS. Cyanide toxicity was induced in 16 New Zealand white rabbits by intravenous infusion. Animals were divided into three groups: controls (n=5) received saline following cyanide, hydroxocobalamin (N=6) following cyanide, and cobinamide (N=5) following cyanide. Cobinamide caused significantly faster and more complete recovery of oxy- and deoxyhemoglobin concentrations in cyanide-exposed animals than hydroxocobalamin- or saline-treated animals, with a recovery time constant of 13.8±7.1 min compared to 75.4±25.1 and 76.4±42.7 min, for hydroxocobalamin- and saline-treated animals, respectively (p<0.0001). This study indicates that cobinamide more rapidly and completely reverses the physiologic effects of cyanide than equimolar doses of cobalamin at the dose used in this study, and CN effects and response can be followed noninvasively using DOS.
Hemoglobin-based oxygen carriers (HBOCs) are solutions of cell-free hemoglobin (Hb) that have been developed for replacement or augmentation of blood transfusion. It is important to monitor in vivo tissue hemoglobin content, total tissue hemoglobin [THb], oxy- and deoxy-hemoglobin concentrations ([OHb], [RHb]), and tissue oxygen saturation (StO2=[OHb]/[THb]×100%) to evaluate effectiveness of HBOC transfusion. We designed and constructed a broadband diffuse optical spectroscopy (DOS) prototype system to measure bulk tissue absorption and scattering spectra between 650 and 1000 nm capable of accurately determining these tissue hemoglobin component concentrations in vivo. Our purpose was to assess the feasibility of using DOS to optically monitor tissue [OHb], [RHb], StO2, and total tissue hemoglobin concentration ([THb]=[OHb]+[RHb]) during HBOC infusion using a rabbit hypovolemic shock model. The DOS prototype probe was placed on the shaved inner thigh muscle of the hind leg to assess concentrations of [OHb], [RHb], [THb], as well as StO2. Hemorrhagic shock was induced in intubated New Zealand white rabbits (N=6) by withdrawing blood via a femoral arterial line to 20% blood loss (10-15 cc/kg). Hemoglobin glutamer-200 (Hb-200) 1:1 volume resuscitation was administered following the hemorrhage. These values were compared against traditional invasive measurements, serum hemoglobin concentration (sHGB), systemic blood pressure, heart rate, and blood gases. DOS revealed increases of [THb], [OHb], and tissue hemoglobin oxygen saturation after Hb-200 infusion, while blood total hemoglobin values continued did not increase; we speculate, due to hyperosmolality induced hemodilution. DOS enables noninvasive in vivo monitoring of tissue hemoglobin and oxygenation parameters during shock and volume expansion with HBOC and potentially enables the assessment of efficacy of resuscitation efforts using artificial blood substitutes.
We demonstrate noninvasive near-infrared diffuse optical spectroscopy (DOS) measurements of tissue hemoglobin contents that can track progressive reductions in central blood volume in human volunteers. Measurements of mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV), and cardiac output (Q) are obtained in ten healthy human subjects during baseline supine rest and exposure to progressive reductions of central blood volume produced by application of lower body negative pressure (LBNP). Simultaneous quantitative noninvasive measurements of tissue oxyhemoglobin (OHb), deoxyhemoglobin (RHb), total hemoglobin concentration (THb), and tissue hemoglobin oxygen saturation (StO2) are performed throughout LBNP application using broadband DOS. As progressively increasing amounts of LBNP are applied, HR increases, and MAP, SV, and Q decrease (p<0.001). OHb, StO2, and THb decrease (p<0.001) in correlation with progressive increases in LBNP, while tissue RHb remained relatively constant (p=0.378). The average fractional changes from baseline values in DOS OHb (fOHb) correlate closely with independently measured changes in SV (r2=0.95) and Q (r2=0.98) during LBNP. Quantitative noninvasive broadband DOS measurements of tissue hemoglobin parameters of peripheral perfusion are capable of detecting progressive reductions in central blood volume, and appear to be sensitive markers of early hypoperfusion associated with hemorrhage as simulated by LBNP.
The purpose of this study is to demonstrate the feasibility of broadband diffuse optical spectroscopy (DOS) for noninvasive optical monitoring of differentiating patterns of total tissue hemoglobin (THC), oxy- (OxyHb), and deoxyhemoglobin (DeOxyHb) concentrations during hypovolemic shock and subsequent fluid replacement with saline and whole blood. The goal of this DOS application is to determine the efficacy of resuscitation efforts at the tissue level rather than currently available indirect and invasive measurements of hemodynamic parameters. 16 New Zealand white rabbits are hemorrhaged 20% of their total blood volume. In resuscitated animals, shed blood volume is replaced with equal volume of crystalloid or whole blood (five animals each). Physiological variables (cardiac output, mean arterial pressure, systemic vascular resistance, hematocrit) are measured invasively, while (OxyHb) and (DeOxyHb) are measured during the interventions using broadband DOS. During the pure hypovolemic hemorrhages, the decrease in THC is mainly due to the decrease in (OxyHb), since the decrease in THC due to blood loss results in decreased tissue perfusion, with a resultant increased tissue extraction of oxygen. The hemorrhage with the whole blood resuscitation model shows significant changes in (OxyHb) during resuscitation phases due to the higher oxygen carrying capacity of whole blood, as opposed to the limited volume replacement effects and the decreased tissue oxygen content from the euvolemic anemia of the saline resuscitation. Broadband DOS noninvasive optical monitoring reveals distinct patterns of total tissue hemoglobin, oxy-, and deoxyhemoglobin during hemorrhage. Further studies are needed to confirm potential clinical utility and accuracy under more complex clinical conditions in animal models and patients.
Recently techniques for two dimensional (2D) or three dimensional (3D) image engraving inside crystal have been developed utilizing its transparency and high refractive index. However, due to the low tolerance against shock, heaviness and high cost of crystal, poymethyl methacryslate (PMMA) can be an attractive alternative for the laser engraving because PMMA has comparable transparency and refractive index to crystal while it is much easier to process. In this paper, we present the preliminary evaluation of PMMA as laser engraving material, potentially replacing crystal. For the comparative evaluation of crystal and PMMA, we used a 3D Laser Engraving System with a Q-switched 2nd harmonic Nd:YAG laser. Pulse energy and repetition rate of Nd:YAG laser were 26.9 mJ and 50 ~ 60 Hz, respectively to produce dot engravings inside crystal and PMMA. Also, the pulse duration time was less than 10 ns. We observed the size and shape of engraved points inside both material and resulting image formation depending on the distance between points (100 ~ 150 μm) as a function of laser power output. For the surface image comparison, an optical microscopy was used, and the cross sectional views of individual points were scanned every 10 μm using an optical coherence tomography (OCT) system. Our results demonstrate that laser engraving inside PMMA created better defined image formation from pure melting process rather than from cracking process inside crystal. We also present optimal 3D laser engraving conditions for PMMA as an alternative material to improve upon crystal's disadvantages.
Near-IR biomedical optical imaging consists of imaging interior volumes on the basis of optical property contrast from measurement conducted at the air-tissue interface. However, the ability to optically image or detect diseased tissue volumes located deep within tissues depends upon the contrast provided by differences in absorption and scattering. The exogenous contrast offered by fluorescent contrast agents may be superior to that provided by nonfluorescing, light-absorbing compounds, when the optical measurement are conducted with frequency-domain techniques. However, the reconstruction of internal fluorescent properties of quantum efficiency and lifetime has been difficult, especially when the finite partitioning of fluorescent compounds takes place between normal and diseased tissues. Also, the correct absorption coefficient map is required for the successful reconstruction of lifetime. Herein we present a novel fluorescence-enhanced imaging algorithm for frequency-domain photon migration measurements imaging differs in that it utilizes measurements of generated fluorescent wave instead of scattered excitation wave. Using synthetic data sets, we demonstrate fluorescence-enhanced imaging using FDA approved fluorescent agent. Indocyanine Green. Our results show the fluorescence-enhanced imaging algorithm works well up to 10:1 dye uptake ratio, and it is relatively insensitive to measurement noise. In addition, we present the lifetime reconstruction with a modified fluorescence-enhanced imaging technique.
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