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Biomedical subjects

Matthew Brenner

Publications and source records attributed to Matthew Brenner.

10 recordsLinked to original sources

Noninvasive in vivo monitoring of methemoglobin formation and reduction with broadband diffuse optical spectroscopy.

We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy (DOS). Broadband DOS combines multifrequency frequency-domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations (denoted by brackets) of methemoglobin ([MetHb]), deoxyhemoglobin ([Hb-R]), and oxyhemoglobin ([HbO2]) were determined from absorption spectra acquired in "real time" during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 microM, representing 2.2 to 14.9% of the total hemoglobin content (%MetHb). These values agreed well with on-site ex vivo cooximetry data (r2= 0.902, P < 0.0001, n = 4). The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue (MB). As little as 10 nM changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations ([Hb-R], [HbO2], [H2O], and [MB]) despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models.

Animals↗

Fiber-optic-bundle-based optical coherence tomography.

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.

Animals↗

In vivo endoscopic optical coherence tomography by use of a rotational microelectromechanical system probe.

A novel endoscopic optical coherence tomography probe was designed and constructed with a 1.9-mm microelectromechanical system (MEMS) motor. The new MEMS endoscopic probe design eliminates the need to couple the rotational energy from the proximal to the distal end of the probe. Furthermore, the endoscopic probe's sheath and fiber have the advantages of having a much smaller diameter and being more flexible than traditional endoscopes since no reinforcement is needed to couple the rotational torque. At the distal end, a prism mounted on a micromotor deflects the light rays to create a transverse circular-scanning pathway. Because our MEMS scanner does not require the coupling of a rotational single-mode fiber, a high scanning speed is possible while eliminating unstable optical signals caused by nonuniform coupling.

Anatomy, Cross-Sectional↗

Feasibility study of normal and septic tracheal imaging using optical coherence tomography.

BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) is an imaging technology that may be adapted for use with flexible fiberoptic bronchoscopy, potentially allowing it to play an important role in pulmonary diagnostics. The goal of this study was to evaluate the feasibility of OCT to image tracheal pathology. STUDY DESIGN/MATERIALS AND METHODS: Tracheas were harvested from normal and septic New Zealand White rabbits and imaged using OCT. Two delivery devices were employed. One was a moving stage with an objective lens and collimator, the other a linear scanning flexible fiberoptic catheter using a GRIN lens and prism for endoscopic OCT. After OCT images were obtained from normal and septic tracheas, the excised tissues were prepared for standard histologic examination. Areas imaged by OCT were compared with corresponding histology slides. RESULTS: OCT images demonstrated in detail tracheal sub-surface structures such as the epithelium, lamina propria, submucosa, and cartilage. The appearance of structures imaged by OCT corresponded very well with histologic pictures obtained by light microscopy. The OCT images from septic tracheas showed marked swelling of the mucosal and submucosal layers. Such pathology was equally imaged by either the moving stage or fiberoptic catheter for endoscopic OCT. CONCLUSIONS: OCT images of the trachea can distinguish many sub-surface structural features usually requiring biopsy and light microscopy for visualization. Marked differences between normal and septic trachea were apparent in OCT images. In the future, OCT may be a valuable tool for evaluating tracheal pathology in situ with high image resolution.

Animals↗

In vivo optical coherence tomography for the diagnosis of oral malignancy.

BACKGROUND AND OBJECTIVE: Oral cancer results in 10,000 U.S. deaths annually. Improved highly sensitive diagnostics allowing early detection of oral cancer would benefit patient survival and quality of life. Objective was to investigate in vivo non-invasive optical coherence tomography (OCT) techniques for imaging and diagnosing neoplasia-related epithelial, sub-epithelial changes throughout carcinogenesis. STUDY DESIGN/MATERIALS AND METHODS: In the standard hamster cheek pouch model for oral carcinogenesis (n = 36), in vivo OCT was used to image epithelial and sub-epithelial change. OCT- and histopathology-based diagnoses on a scale of 0 (healthy) to 6 (squamous cell carcinoma, SCC) were performed at all stages throughout carcinogenesis by two blinded investigators. RESULTS: Epithelial, sub-epithelial structures were clearly discernible using OCT. OCT diagnosis agreed with the histopathological gold standard in 80% of readings. CONCLUSION: In vivo OCT demonstrates excellent potential as a diagnostic tool in the oral cavity.

Animals↗

Noninvasive monitoring of hemodynamic stress using quantitative near-infrared frequency-domain photon migration spectroscopy.

Hemorrhagic hypovolemia and inotropic agent administration were used to manipulate cardiac output (CO) and oxygen delivery in rabbits to investigate the correlation between noninvasive frequency domain photon migration (FDPM) spectroscopy and invasive hemodynamic monitoring parameters. Frequency-domain photon migration provides quantitative measurements of light absorption and reduced scattering (mu(a) and mu(s)(prime prime or minute), respectively) in tissue. Wavelength dependent mu(a) values were used to calculate in vivo tissue concentration of deoxyhemoglobin [Hb], oxyhemoglobin [HbO(2)], total hemoglobin [TotHb], and water [H(2)O] as well as mixed arterial-venous oxygen saturation (S(t)O(2)) in tissue. FDPM-derived physiologic properties were correlated with invasive measurements of CO and mean pulmonary artery pressure (mPAP), FDPM-derived [TotHb] and S(t) O(2) correlated significantly with hemorrhaged volume (HV), mPAP, and CO. Correlation coefficients for [TotHb] vs HV, mPAP, and CO were -0.77, 0.86, and 0.70, respectively. Correlation coefficients of S(t)O( 2) vs HV, mPAP, and CO were -0.71, 0.55, and 0.61, respectively. Dobutamine induced changes resulted in correlation coefficients between FDPM-derived and invasively measured physiologic parameters that are comparable to those induced by hypovolemia. FDPM spectroscopy is sensitive to changes in mPAP and CO of as little as 15%. These results suggest that FDPM spectroscopy may be used in clinical settings to noninvasively monitor central hemodynamic parameters and to directly assess oxygenation of tissues.

Animals↗

Effects of a novel implantable elastomer device for lung volume reduction surgery in a rabbit model of elastase-induced emphysema.

OBJECTIVES: There is intense interest in lung volume reduction surgery (LVRS) for treatment of severe symptomatic emphysema. LVRS results in objective and subjective improvement in lung function in selected patients. However, LVRS is complicated by substantial morbidity, including prolonged pulmonary air leak associated with resection of emphysematous lung tissue. In this study, we investigated the use of a novel implanted silicone elastomer device that reduces lung volume without surgical resection, in a previously reported emphysematous animal model. The purpose of this investigation was to determine the applicability, physiologic effects, complications, and air-leak results of this lung volume reducer (LVR) approach. DESIGN: Controlled, randomized, prospective animal study. Emphysema was induced in 20 New Zealand white rabbits with three nebulizations of 10,000 U of porcine elastase. After 6 weeks, the animals were randomized to control sham surgery (n = 10) vs implanted silicone elastomer LVR (n = 10) treatment groups. Lung function, including helium-dilution lung volumes, static respiratory system compliance curves, and diffusion capacity of the lung for carbon monoxide (DLCO), was measured at baseline, following emphysema induction (week 6), and when the animals were killed (1 week after LVR or sham surgery). Histologic evaluation was performed in all lung specimens after fixation. RESULTS: Moderate emphysema developed after elastase nebulization, assessed by lung function and postmortem histology. Functional residual capacity (FRC) and an upward shift of lung compliance curves was observed with development of emphysema at 6 weeks (p < 0.05). Following LVR, FRC decreased (p = 0.005) and compliance curves shifted back downward (p = 0.002), without reduction in DLCO. There was no change in control sham animals. DLCO did not change in either group. CONCLUSIONS: In this short-term, randomized, controlled animal model study, the implantable LVR approach produced safe and effective lung volume reduction without tissue resection in the treated animals. The implant procedure produced minimal morbidity, no mortality, and no observed air-leak complications in the treated animals. Limitations include the short-term follow-up and moderate degree of emphysema in this animal model. Further research is required to assess long-term effects and complications of this method for lung volume reduction.

Animals↗

Optical coherence tomography of malignancy in hamster cheek pouches.

Optical coherence tomography (OCT)/optical Doppler tomography (ODT) provides real-time in vivo high-resolution (10-microm) imaging of tissues and real-time spatially resolved blood flow in microvasculature. Hamster cheek pouches with induced dysplasia and malignancies were imaged with OCT/ODT to assess the potential for application to airway malignancy. In 22 Golden Syrian hamsters, 0.5% 9,10-dimethyl-1,2-benzanthracene induces carcinogenesis over 10 weeks in right side cheek pouches; the left side three served as controls. The cheek pouches are imaged in vivo prior to sacrifice, and in vitro after excision, using a prototype 1310-nm broadband superluminescent diode based OCT/ODT device. Images are compared to standard histopathology. OCT imaging offers good resolution of the hamster cheek pouches to depths of 1 to 3 mm and paralleled histologic images. The feasibility of high-resolution functional imaging is demonstrated in this hamster cheek pouch tumor model. ODT accurately detects vascular change associated with carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Evaluation of tracheal imaging by optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a new technology capable of generating high resolution cross-sectional images of complex tissue in real time. Analogous to ultrasound, OCT measures backscattered light intensity using coherence interferometery to construct topographical images of complex tissue. Since OCT uses infrared light rather than acoustic waves, its spatial resolution is exceptionally high (2-10 microm). Recent advances in data acquisition, analysis, and processing enable real-time imaging, and make OCT a potentially valuable tool for pulmonary airway diagnostic applications, including assisting directed airway biopsies. OBJECTIVE: This study evaluates feasibility of OCT for delineating proximal airway microstructures in various animal as well as human tracheas. METHODS: Excised trachea samples from New Zealand white rabbits, Duroc pigs, and human trachea were imaged using a compact, 1,300-nm broad-band superluminescent-diode-based prototype fiber OCT device we constructed. The resulting structural OCT images were compared to conventional hematoxilin and eosin (HE) stained histological sections from the same samples. RESULTS: OCT was able to delineate microstructures such as the epithelium, mucosa, cartilage, and glands in all samples. CONCLUSION: These findings suggest that integration of OCT with flexible fiberoptic bronchoscopy could enhance pulmonary diagnostic medicine and detection of pathologic tissue changes in various respiratory diseases.

Animals↗