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ABSTRACT: 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.
Journal of Biomedical Optics 10/2012; 17(10):105005-1. · 3.16 Impact Factor
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Jiechen Yin,
Xiang Li,
Joe Jing,
Jiawen Li, David Mukai,
Sari Mahon,
Ahmad Edris,
Khiet Hoang,
K Kirk Shung,
Matthew Brenner,
Jagat Narula,
Qifa Zhou,
Zhongping Chen
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ABSTRACT: We have developed a miniature integrated optical coherence tomography (OCT) ultrasound (US) probing system for intravascular imaging applications. In the OCT probe, the light coming out of a single mode fiber is focused by a gradient-index lens and then reflected by a right-angle prism from the side of the probe into the sample. It was combined with a 35 MHz PMN-PT side-viewing ultrasound transducer to obtain the ultrasound image as well. The OCT and ultrasound probes were integrated as a single probe to obtain OCT and ultrasound images simultaneously. The integrated probe has an outer diameter of 0.69 mm which, to our knowledge, is the smallest integrated OCT-US probe reported. Fast data acquisition and processing was implemented for real-time imaging. In vitro OCT and US images of human coronary artery with pathology, as well as in vivo images of normal rabbit abdominal aorta, were obtained using the integrated OCT-US probe to demonstrate its capability.
Journal of Biomedical Optics 06/2011; 16(6):060505. · 3.16 Impact Factor
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Sang-Won Lee,
Andrew E Heidary,
David Yoon, David Mukai,
Tirunelveli Ramalingam,
Sari Mahon,
Jiechen Yin,
Joseph Jing,
Gangjun Liu,
Zhongping Chen,
Matthew Brenner
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ABSTRACT: Smoke inhalation injury is frequently accompanied by cyanide poisoning that may result in substantial morbidity and mortality, and methods are needed to quantitatively determine extent of airway injury. We utilized a 3-D endoscopic frequency-domain optical coherence tomography (FD-OCT) constructed with a swept-source laser to investigate morphological airway changes following smoke and cyanide exposure in rabbits. The thickness of the mucosal area between the epithelium and cartilage in the airway was measured and quantified. 3-D endoscopic FD-OCT was able to detect significant increases in the thickness of the tracheal walls of the rabbit beginning almost immediately after smoke inhalation injuries which were similar to those with combined smoke and cyanide poisoning.
Biomedical Optics Express 01/2011; 2(2):243-54. · 2.33 Impact Factor
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ABSTRACT: Laser-induced damage of tracheal wall microstructures might contribute to recurrence after bronchoscopic treatment of tracheal strictures. The purpose of this study was to demonstrate how multimodal imaging using white light bronchoscopy (WLB), endobronchial ultrasound (EBUS), and optical coherence tomography (OCT) might identify in vivo airway wall changes before and resulting from Nd:YAG laser ablation and dilation of tracheal stenosis.
Case study.
Commercially available WLB, high frequency EBUS using a 20-MHz radial probe and time-domain, frontal imaging OCT systems were used to characterize the extent, morphology, and airway wall microstructures at the area of hypertrophic fibrotic tissue formation before, during and after treatment of postintubation tracheal stenosis.
WLB revealed the location of a complex, extensive, severe stricture. EBUS showed a homogeneous layer overlying a hyperechogenic layer corresponding to disrupted cartilage. OCT showed a homogeneous light backscattering layer and absence of layered microstructures, confirming absence in close proximity of normal airway wall. After laser ablation, OCT of charred tissue showed high backscattering and shadowing artifacts. OCT of noncharred tissue showed a thinner, homogeneous, light backscattering layer. EBUS showed thinner but persistent hypertrophic tissue suggesting incomplete treatment. WLB revealed improved airway patency postprocedure and recurrence 3 weeks later.
EBUS identified cartilage disruption and residual hypertrophic tissue, the evidence of which might contribute to recurrence. OCT revealed homogeneous light backscaterring representing persistent noncharred hypertrophic tissues but it did not visualize cartilage disruption. Future studies are warranted to confirm whether these technologies can help guide bronchoscopic treatments.
The Laryngoscope 09/2010; 120(9):1840-6. · 1.75 Impact Factor
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Matthew Brenner,
Jae G Kim,
Sari B Mahon,
Jangwoen Lee,
Kelly A Kreuter,
William Blackledge, David Mukai,
Steve Patterson,
Othman Mohammad,
Vijay S Sharma,
Gerry R Boss
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ABSTRACT: Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B(12)) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigate the use of intramuscular cobinamide sulfite to reverse cyanide toxicity-induced physiologic changes in a sublethal cyanide exposure animal model and determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity.
New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous-wave near-infrared spectroscopy monitoring of tissue oxyhemoglobin and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5).
Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and within deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system occurred within a mean of 1,032 minutes in the control group and 9 minutes in the cobinamide group, with a difference of 1,023 minutes (95% confidence interval 116 to 1,874 minutes). In muscle tissue, recovery times were 76 and 24 minutes, with a difference of 52 minutes (95% confidence interval 7 to 98 minutes). RBC cyanide levels returned toward normal significantly faster in cobinamide sulfite-treated animals than in control animals.
Intramuscular cobinamide sulfite rapidly and effectively reverses the physiologic effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can be developed for mass casualty cyanide exposures.
Annals of emergency medicine 04/2010; 55(4):352-63. · 4.23 Impact Factor
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Jangwoen Lee,
Kelly A Keuter,
Jae Kim,
Andrew Tran,
Amit Uppal, David Mukai,
Sari Brenner Mahon,
Leopoldo C Cancio,
Andriy Batchinsky,
Bruce J Tromberg,
Matthew Brenner
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ABSTRACT: Currently, no reliable noninvasive methods exist for monitoring the severity of in vivo cyanide (CN) toxicity, treatment, and resulting physiological changes. We developed a broadband diffuse optical spectroscopy (DOS) system to measure bulk tissue absorption and scattering. DOS was used to optically monitor CN toxicity and treatment with sodium nitrite (NaNO2). To perform experiments, the DOS probe was placed on the hind leg of rabbits. A sodium CN solution was infused intravenously. DOS and concurrent physiologic measurements were obtained. After completion of CN infusion, NaNO2 was infused to induce methemoglobinemia (MetHb). During infusion of CN, blood gas measurements showed an increase in venous partial pressure of oxygen (pO2), and following reversal, venous pO2 values decreased. DOS measurements demonstrated corresponding changes in hemoglobin oxygenation states and redox states of cytochrome-c oxidase (CcO) during CN infusion and NaNO2 treatment. Therefore, DOS enables detection and monitoring of CN toxicity and treatment with NaNO2.
Military medicine 07/2009; 174(6):615-21. · 0.92 Impact Factor
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ABSTRACT: Concentrated aqueous solutions of hydroxocobalamin (OHCob) are administered intravenously for cyanide poisoning victims, many of whom also have concurrent smoke inhalation. Because of its intense light absorbance in visible wavelengths (absorption peak at 532 nm), we investigate potential interference effects of OHCob on total hemoglobin concentration (tHb), carboxyhemoglobin (COHb), methemoglobin (MetHb), and oxyhemoglobin (Hb-O2) cooximetry measurement values in blood.
In vivo cooximetry measurements were conducted with 3 specific pathogen-free white New Zealand rabbits (3.80+/-0.21 kg) during the intravenous infusion of OHCob (625 mg during a 100-minute period). Resultant changes in tHb, Hb-O2, COHb, and MetHb values were measured and correlated with respect to estimated in vivo OHCob concentrations. In vitro measurements were conducted with rabbit blood to confirm in vivo measurements.
The introduction of OHCob clearly interfered with the cooximetry measurements of each of the hemoglobin component fractions in whole blood and resulted in altered measurement values from the baseline values. The presence of OHCob in blood interferes with cooximetry measurements of COHb, MetHb, and Hb-O2. The increase in measured COHb fraction with increasing concentrations of OHCob was most notable.
The presence of OHCob in blood interferes with cooximetry measurements of COHb, MetHb, and Hb-O2. These effects need to be considered during OHCob treatment of cyanide poisoning, particularly in smoke inhalation victims with potential for concurrent carbon monoxide exposure, because it may lead to potentially erroneous reported COHb levels.
Annals of emergency medicine 07/2007; 49(6):802-5. · 4.23 Impact Factor
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ABSTRACT: Hamster cheek pouches (HCP) with various degrees of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced dysplasia and malignancies were imaged with OCT/ODT in vivo and in vitro to assess the potential for three-dimensional high-resolution optical localization of airway malignancy.
Optical coherence tomography (OCT)/optical doppler tomography (ODT) provide potential capability for real-time in vivo high-resolution (2-20 microm) cross-sectional imaging of tissues and spatially resolved blood flow in microvasculature for pathology diagnostics.
DMBA was applied to the right side of the cheek pouch (HCP), and mineral oil (control) to the left side three times weekly for 10-18 weeks in Syrian Golden Hamsters using a standard protocol for malignancy induction. HCP were imaged in vivo with OCT/ODT as well as in vitro post-excision, using a prototype 1310-nm broadband superluminescent diode-based OCT/ODT device constructed in our laboratory. Three-dimensional images were constructed, and compared to standard and three-dimensional histology hematoxylin and eosin staining.
OCT imaging offered exceptional resolution of the HCP to depths of 1-2 mm and confirmed ability to detect dysplasia and malignancy. Three-dimensional OCT images were readily constructed, allowing visualization of extent and localization of tumor margins. ODT demonstrated increased vascularity in the area of neoplasia. OCT/ODT is a promising new technology for oral airway diagnostics.
Photomedicine and Laser Surgery 07/2006; 24(3):402-9. · 1.25 Impact Factor
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ABSTRACT: In this manuscript, a GRIN (gradient index) lens rod based probe for endoscopic spectral domain optical coherence tomography (OCT) with dynamic focus tracking is presented. Current endoscopic OCT systems have a fixed focal plane or working distance. In contrast, the focus of this endoscopic OCT probe can dynamically be adjusted at a high speed (500 mm/s) without changing reference arm length to obtain high quality OCT images for contact or non-contact tissue applications, or for areas of difficult access for probes. The dynamic focusing range of the probe can be from 0 to 7.5 mm without moving the probe itself. The imaging depth is 2.8 mm and the lateral scanning range is up to 2.7 mm or 4.5 mm (determined by the diameter of different GRIN lens rods). Three dimensional imaging can be performed using this system over an area of tissue corresponding to the GRIN lens surface. The experimental results demonstrate that this GRIN lens rod based OCT system can perform a high quality non-contact in vivo imaging. This rigid OCT probe is solid and can be adapted to safely access internal organs, to perform front or side view imaging with an imaging speed of 8 frames per second, with all moving parts proximal to the GRIN lens, and has great potential for use in extremely compact OCT endoscopes for in vivo imaging in both biological research and clinical applications.
Optics Express 05/2006; 14(8):3238-46. · 3.59 Impact Factor
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ABSTRACT: A fiber-optic-bundle-based optical coherence tomography (OCT) probe method is presented. The experimental results demonstrate this multimode optical fiber-bundle-based OCT system can achieve a lateral resolution of 12 microm and an axial resolution of 10 microm with a superluminescent diode source. This novel OCT imaging approach eliminates any moving parts in the probe and has a primary advantage for use in extremely compact and safe OCT endoscopes for imaging internal organs and great potential to be combined with confocal endoscopic microscopy.
Optics Letters 08/2005; 30(14):1803-5. · 3.40 Impact Factor
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Matthew Brenner,
Kelly Kreuter,
Johnny Ju,
Sari Mahon,
Lillian Tseng, David Mukai,
Tanya Burney,
Shuguang Guo,
Jianping Su,
Andrew Tran,
Andriy Batchinsky,
Leopoldo C Cancio,
Navneet Narula,
Zhongping Chen
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ABSTRACT: Smoke inhalation injury causes acute airway injury that may result in airway compromise with significant morbidity and mortality. We investigate the ability of high resolution endobronchial optical coherence tomography (OCT) to obtain real-time images for quantitatively assessing regional differences between upper tracheal versus lower tracheal and bronchial airway injury responses to smoke inhalation in vivo using a prototype spectral domain (SLD)-OCT system we constructed, and flexible fiber optic probes. 33 New Zealand White rabbits are intubated and mechanically ventilated. The treatment groups are exposed to inhaled smoke. The OCT probe is introduced through the endotracheal tube and maintained in place for 5 to 6 h. Images of airway mucosa and submucosa are obtained at baseline and at specified intervals postexposure. Starting within less than 15 min after smoke inhalation, there is significant airway thickening in the smoke-exposed animals. This is maintained over 5 h of imaging studies. The lower tracheal airway changes, correlating closely with carboxyhemoglobin levels, are much greater than upper tracheal changes. Significant differences are seen in lower trachea and bronchi after acute smoke inhalation compared to upper trachea as measured in vivo by minimally invasive OCT. OCT is capable of quantitatively detecting regional changes in airway swelling following inhalation injury.
Journal of Biomedical Optics 13(3):034001. · 3.16 Impact Factor
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Matthew Brenner,
Kelly Kreuter, David Mukai,
Tanya Burney,
Shuguang Guo,
Jianping Su,
Sari Mahon,
Andrew Tran,
Lillian Tseng,
Johnny Ju,
Zhongping Chen
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ABSTRACT: Optical coherence tomography (OCT) is a micron scale high-resolution optical technology that can provide real-time in vivo images noninvasively. The ability to detect airway mucosal and submucosal injury rapidly will be valuable for a range of pulmonary applications including assessment of acute inhalation smoke and burn injury. OCT has the potential ability to monitor the progression of airway injury changes including edema, hyperemia, and swelling, which are critical clinical components of smoke-inhalation injury. New Zealand white male rabbits exposed to cold smoke from standardized unbleached burned cotton administered during ventilation were monitored for 6 h using a 1.8-mm diameter flexible fiberoptic longitudinal probe that was inserted through the endotracheal tube. The thickness of the epithelial, mucosal, and submucosal layers of the rabbit trachea to the tracheal cartilage was measured using a prototype superluminescent diode OCT system we constructed. OCT was able to detect significant smoke-injury-induced increases in the thickness of the tracheal walls of the rabbit beginning very shortly after smoke administration. Airway wall thickness increased to an average of 120% (+/-33%) of baseline values by 5 h following exposure. OCT is capable of providing real-time, noninvasive images of airway injury changes following smoke exposure. These studies suggest that OCT may have the ability to provide information on potential early indicators of impending smoke-inhalation-induced airway compromise.
Journal of Biomedical Optics 12(5):051701. · 3.16 Impact Factor
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ABSTRACT: We report on the feasibility of rapid, high-resolution, 3-D swept-source optical coherence tomography (SSOCT) to detect early airway injury changes following smoke inhalation exposure in a rabbit model. The SSOCT system obtains 3-D helical scanning using a microelectromechanical system motor-based endoscope. Real-time 2-D data processing and image display at the speed of 20 frames/s are achieved by adopting the technique of parallel computing. Longitudinal images are reconstructed via an image processing algorithm to remove motion artifacts caused by ventilation and pulse. Quantitative analyses of tracheal airway thickness as well as thickness distribution along tracheal circumference are also performed based on the comprehensive 3-D volumetric data.
Journal of Biomedical Optics 14(6):060503. · 3.16 Impact Factor
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Matthew Brenner,
Sari B Mahon,
Jangwoen Lee,
Jae Kim, David Mukai,
Seth Goodman,
Kelly A Kreuter,
Rebecca Ahdout,
Othman Mohammad,
Vijay S Sharma,
William Blackledge,
Gerry R Boss
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ABSTRACT: 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.
Journal of Biomedical Optics 15(1):017001. · 3.16 Impact Factor
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ABSTRACT: The purpose of this study was to develop a dynamic tunable focal distance graded-refractive-index lens rod-based high-speed 3-D swept-source (SS) optical coherence tomography (OCT) endoscopic system and demonstrate real-time in vivo, high-resolution (10-microm) imaging of pleural-based malignancies in an animal model. The GRIN lens-based 3-D SS OCT system, which images at 39 fps with 512 A-lines per frame, was able to capture images of and detect abnormalities during thoracoscopy in the thoracic cavity, including the pleura, chest wall, pericardium, and the lungs. The abnormalities were confirmed by histological evaluation and compared to OCT findings. The dynamic tunable focal distance range and rapid speed of the probe and SS prototype OCT system enabled this first-reported application of in vivo 3-D thoracoscopic imaging of pleural-based malignancies. The imaging probe of the system was found to be easily adaptable to various sites within the thoracic cavity and can be readily adapted to other sites, including rigid airway endoscopic examinations.
Journal of Biomedical Optics 14(6):064045. · 3.16 Impact Factor
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ABSTRACT: 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 (S(t)O(2)=[OHb][THb]x100%) 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], S(t)O(2), 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 S(t)O(2). 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 cckg). 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.
Journal of Biomedical Optics 14(4):044027. · 3.16 Impact Factor
