Near infrared autofluorescence augmentation of optical coherence tomography for diagnosis of coronary atherosclerosis

Thesis (Ph.D.)--Boston UniversityCoronary artery disease accounts for nearly 50% of cardiovascular disease, the leading cause of death in the United States. The progression of atherosclerotic plaque is not yet fully understood. Histopathologic analysis of cadaver coronary plaques has suggested that certain subsets of coronary lesions, the vulnerable plaques, predispose patients to myocardial infarction. Prospective identification and treatment of vulnerable plaques has emerged as an important future goal for intravascular imaging and intervention. However, no single imaging modality has been shown to be capable of definitively identifying these lesions. Optical coherence tomography is a catheter-based imaging method that rapidly acquires three-dimensional images of coronary artery wall microstructure. While OCT has been documented to be capable of visualizing morphologic features associated with vulnerable plaques, it has not been shown to identify necrotic core or other putative chemicals/molecules associated with plaque progression and rupture. One solution is to add a secondary modality to OCT which detects molecules specific to necrotic cores. While conducting bench top spectroscopy measurements, our laboratory discovered that the intensity of near-infrared autofluorescence (NIRAF) is associated with plaque types. Using benchtop spectroscopy, this dissertation research established the relationship between the NIRAF signal intensity and spectral shape and atherosclerosis, and demonstrated its potential to differentiate necrotic core plaques from other arterial lesions. In addition to these spectroscopy-disease correlations, this thesis describes research conducted to identify the chemical/molecular origin of the NIRAF signal, using histopathology, confocal microscopy, spectroscopy, and chemical synthesis. The results indicate that protein modification in necrotic core is a potential mechanism for high NIRAF in advanced plaques. To translate OCT-NIRAF clinically, this dissertation describes the design of a double clad fiber that enables catheter-based detection of both OCT and NIRAF and a safety study to demonstrate that NIRAF excitation does not damage the artery wall. A preclinical OCT-NIRAF catheter was fabricated and used to image human coronary arteries ex vivo. These data showed that vulnerable plaques can potentially be identified using intracoronary OCT-NIRAF. The sum total of results from this thesis reseatch demonstrate the feasibility of conducting OCT-NIRAF imaging in human patients for the prospective identification ofvulnerable coronary plaques

SeaWiFS technical report series. Volume 5: Ocean optics protocols for SeaWiFS validation

Protocols are presented for measuring optical properties, and other environmental variables, to validate the radiometric performance of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS), and to develop and validate bio-optical algorithms for use with SeaWiFS data. The protocols are intended to establish foundations for a measurement strategy to verify the challenging SeaWiFS accuracy goals of 5 percent in water-leaving radiances and 35 percent in chlorophyll alpha concentration. The protocols first specify the variables which must be measured, and briefly review rationale. Subsequent chapters cover detailed protocols for instrument performance specifications, characterizing and calibration instruments, methods of making measurements in the field, and methods of data analysis. These protocols were developed at a workshop sponsored by the SeaWiFS Project Office (SPO) and held at the Naval Postgraduate School in Monterey, California (9-12 April, 1991). This report is the proceedings of that workshop, as interpreted and expanded by the authors and reviewed by workshop participants and other members of the bio-optical research community. The protocols are a first prescription to approach unprecedented measurement accuracies implied by the SeaWiFS goals, and research and development are needed to improve the state-of-the-art in specific areas. The protocols should be periodically revised to reflect technical advances during the SeaWiFS Project cycle

Dedicated JPSS VIIRS Ocean Color Calibration/Validation Cruise

The NOAA/STAR ocean color team is focused on “end-to-end” production of high quality satellite ocean color products. In situ validation of satellite data is essential to produce the high quality, “fit for purpose” remotely sensed ocean color products that are required and expected by all NOAA line offices, as well as by external (both applied and research) users. In addition to serving the needs of its diverse users within the U.S., NOAA has an ever increasing role in supporting the international ocean color community and is actively engaged in the International Ocean-Colour Coordinating Group (IOCCG). The IOCCG, along with the Committee on Earth Observation Satellites (CEOS) Ocean Colour Radiometry Virtual Constellation (OCR-VC), is developing the International Network for Sensor Inter-comparison and Uncertainty assessment for Ocean Color Radiometry (INSITU-OCR). The INSITU-OCR has identified, amongst other issues, the crucial need for sustained in situ observations for product validation, with longterm measurement programs established and maintained beyond any individual mission. Recently, the NOAA/STAR Ocean Color Team has been making in situ validation measurements continually since the launch in fall 2011 of the Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polar-orbiting Partnership (SNPP) platform, part of the U.S. Joint Polar Satellite System (JPSS) program. NOAA ship time for the purpose of ocean color validation, however, had never been allocated until the cruise described herein. As the institutional lead for this cruise, NOAA/STAR invited external collaborators based on scientific objectives and existing institutional collaborations. The invited collaborators are all acknowledged professionals in the ocean color remote sensing community. Most of the cruise principal investigators (PIs) are also PIs of the VIIRS Ocean Color Calibration and Validation (Cal/Val) team, including groups from Stennis Space Center/Naval Research Laboratory (SSC/NRL) and the University of Southern Mississippi (USM); City College of New York (CCNY); University of Massachusetts Boston (UMB); University of South Florida (USF); University of Miami (U. Miami); and, the National Institute of Standards and Technology (NIST). These Cal/Val PIs participated directly, sent qualified researchers from their labs/groups, or else contributed specific instruments or equipment. Some of the cruise PIs are not part of the NOAA VIIRS Ocean Color Cal/Val team but were chosen to complement and augment the strengths of the Cal/Val team participants. Outside investigator groups included NASA Goddard Space Flight Center (NASA/GSFC), Lamont-Doherty Earth Observatory at Columbia University (LDEO), and the Joint Research Centre of the European Commission (JRC). This report documents the November 2014 cruise off the U.S. East Coast aboard the NOAA Ship Nancy Foster. This cruise was the first dedicated ocean color validation cruise to be supported by the NOAA Office of Marine and Air Operations (OMAO). A second OMAO-supported cruise aboard the Nancy Foster is being planned for late 2015. We at NOAA/STAR are looking forward to continuing dedicated ocean color validation cruises, supported by OMAO on NOAA vessels, on an annual basis in support of JPSS VIIRS on SNPP, J-1, J-2 and other forthcoming satellite ocean color missions from the U.S as well as other countries. We also look forward to working with the U.S. and the international ocean community for improving our understanding of global ocean optical, biological, and biogeochemical properties.JRC.H.1-Water Resource

Determination of Caries Lesion Activity: Reflection and Roughness for Characterization of Caries Progression

Used by permission. © Operative Dentistry, Inc. Transmission or reproduction of protected items beyond that allowed by fair use requires the written permission of Operative Dentistry, Inc.Caries lesion progression is difficult to determine with visual and tactile examinations. The hypothesis of this study was that reflection and roughness measurements could determine caries progression. Ground/polished sound human enamel specimens were analyzed at baseline (sound) and after two four-day demineralization periods for reflection using optical reflectometry (ORef) and for roughness using optical surface profilometry (SPro). Specimens were demineralized using a microbial–Streptococcus mutans aries model. Comparisons among the periods for ORef and SPro were performed using repeated measures analysis of variance. Two-sample t-tests were used for differences in transverse microradiography. The integrated mineral loss and depth of the four-day demineralization period were significantly smaller than those for the eight-day demineralization period (p<0.01). With increased demineralization time, reflection was significantly decreased and roughness was significantly increased (p<0.01). Correlation between ORef and SPro was moderate (r=−0.63). Both reflection and roughness can be characterized for nondestructive longitudinal assessment of caries lesion progression

Infrared attenuated total reflection spectroscopy for monitoring biological systems

Mid-infrared (MIR) spectroscopy has been recognized as an important analytical technique, and is widely applied for qualitative and quantitative analysis of materials with an increasing interest in addressing complex organic or biologic constituents. In the presented thesis, (a) the fundamental principles for IR spectroscopic applications via in vivo catheters in combination with multivariate data analysis technique were developed, and (b) the combination with a second analytical technique ¨C scanning electrochemical microscopy (SECM) - for enhancing the information obtained at complex or frequently changing matrices was demonstrated. The first part of this thesis focused on the combination of different MIR measurment techniques with specific focus on evanescent field absorption spectroscopy along with multivariate data analysis methods, for the discrimination of atherosclerotic and normal rabbit aorta tissues. Atherosclerotic and normal rabbit aorta tissues are characterized by marked differences in chemical composition governed by their water, lipid, and protein content. Strongly overlapping infrared absorption features of the different constituents and the complexity of the tissue matrix render the direct evaluation of molecular spectroscopic characteristics obtained from IR measurements challenging for classification. We have successfully applied multivariate data analysis and classification techniques based on principal component analysis (PCA), partial least squares regression (PLS), and linear discriminant analysis (LDA) to IR spectroscopic data obtained by infrared attenuated total reflectance (IR-ATR) measurements, reflection IR microscopy, and a recently developed IR-ATR catheter prototype for future in vivo diagnostic applications. Training and test data were collected ex vivo at atherosclerotic and normal rabbit aorta samples. The successful classification results at atherosclerotic and normal aorta samples utilizing the developed data evaluation routines reveals the potential of IR spectroscopy combined with multivariate classification strategies for in vitro, and ¨C in future - in vivo applications. The second part of this thesis aimed at the development of a novel multifunctional analytical platform by combining SECM with single-bounce IR-ATR spectroscopy for in situ studies of electrochemically active or electrochemically induced processes at the IR waveguide surface via simultaneous evanescent field absorption spectroscopy. The utility of the developed SECM-IR-ATR platform was demonstrated by spectroscopically monitoring microstructured polymer depositions induced via feedback mode SECM experiments using a 25μm Pt disk ultramicroelectrode (UME). The surface of a ZnSe ATR crystal was coated with a thin layer of 2,5-di-(2-thienyl)-pyrrole (SNS), which was then polymerized in a Ru(bpy) ₃ ² ⁺-mediated feedback mode SECM experiment. The polymerization reaction was simultaneously spectroscopically monitored by recording the absorption intensity changes of specific IR bands characteristic for SNS, thereby providing information on the polymerization progress, mechanism, and level of surface modification. Furthermore, a novel current-independent approach mechanism for positioning the UME in aqueous electrolyte solution was demonstrated by monitoring IR absorption changes of borosilicate glass (BSG) shielding the UME, and of water within the penetration depth of the evanescent field.Ph.D.Committee Chair: Mizaikoff, Boris; Committee Member: Fernandez, Facundo; Committee Member: Orlando, Thomas; Committee Member: Palmer. Richard; Committee Member: Whetten, Rober

ANISOTROPIC POLARIZED LIGHT SCATTER AND MOLECULAR FACTOR COMPUTING IN PHARMACEUTICAL CLEANING VALIDATION AND BIOMEDICAL SPECTROSCOPY

Spectroscopy and other optical methods can often be employed with limited or no sample preparation, making them well suited for in situ and in vivo analysis. This dissertation focuses on the use of a near-infrared spectroscopy (NIRS) and polarized light scatter for two such applications: the assessment of cardiovascular disease, and the validation of cleaning processes for pharmaceutical equipment.There is a need for more effective in vivo techniques for assessing intravascular disorders, such as aortic aneurysms and vulnerable atherosclerotic plaques. These, and other cardiovascular disorders, are often associated with structural remodeling of vascular walls. NIRS has previously been demonstrated as an effective technique for the analysis of intact biological samples. In this research, traditional NIRS is used in the analysis of aortic tissue samples from a murine knockout model that develops abdominal aortic aneurysms (AAAs) following infusion of angiotensin II. Effective application of NIRS in vivo, however, requires a departure from traditional instrumental principles. Toward this end, the groundwork for a fiber optic-based catheter system employing a novel optical encoding technique, termed molecular factor computing (MFC), was developed for differentiating cholesterol, collagen and elastin through intervening red blood cell solutions. In MFC, the transmission spectra of chemical compounds are used to collect measurements directly correlated to the desired sample information.Pharmaceutical cleaning validation is another field that can greatly benefit from novel analytical methods. Conventionally cleaning validation is accomplished through surface residue sampling followed by analysis using a traditional analytical method. Drawbacks to this approach include cost, analysis time, and uncertainties associated with the sampling and extraction methods. This research explores the development of in situ cleaning validation methods to eliminate these issues. The use of light scatter and polarization was investigated for the detection and quantification of surface residues. Although effective, the ability to discriminate between residues was not established with these techniques. With that aim in mind, the differentiation of surface residues using NIRS and MFC was also investigated

Self-cleaning and antibiofouling enamel surface by slippery liquid-infused technique.

We aimed to create a slippery liquid-infused enamel surface with antibiofouling property to prevent dental biofilm/plaque formation. First, a micro/nanoporous enamel surface was obtained by 37% phosphoric acid etching. The surface was then functionalized by hydrophobic low-surface energy heptadecafluoro-1,1,2,2-tetra- hydrodecyltrichlorosilane. Subsequent infusion of fluorocarbon lubricants (Fluorinert FC-70) into the polyfluoroalkyl-silanized rough surface resulted in an enamel surface with slippery liquid-infused porous surface (SLIPS). The results of water contact angle measurement, diffuse-reflectance Fourier transform infrared spectroscopy, and atomic force microscope confirmed that the SLIPS was successfully constructed on the enamel surface. The antibiofouling property of the SLIPS was evaluated by the adsorption of salivary protein of mucin and Streptococcus mutans in vitro, as well as dental biofilm formation using a rabbit model in vivo. The results showed that the SLIPS on the enamel surface significantly inhibited mucin adhesion and S. mutans biofilm formation in vitro, and inhibited dental plaque formation in vivo.published_or_final_versio

Application of Photoacoustic Methods and Confocal Microscopy for Monitoring of Therapeutic Response in Plaque Psoriasis

Psoriasis is prone to relapses and requires long-term therapy that may induce a range of adverse effects; therefore, an efficient and early detection of relapses is desirable. In this study, photoacoustic imaging and confocal laser scanning microscopic (CLSM) methods were investigated for their suitability in psoriasis follow-up examinations. Using a high-resolution photoacoustic system, the vascular structures of 11 psoriatic patients and 6 healthy volunteers were investigated. No differences were detected with respect to the average vessel diameter and vasculature per unit volume in the tissue of healthy volunteers and non-lesional and lesional skin areas of psoriatic patients. By means of CLSM, the diameters of the dermal papillae of 6 volunteers and 6 psoriatic patients were determined. The diameters of the dermal papillae of the healthy volunteers (0.074 +/- 0.006 mm) revealed no significant difference when compared to non-lesional skin areas of psoriatic patients (0.079 +/- 0.005 mm). The results obtained for the lesions in psoriatic patients showed a significant difference (Wilcoxon test, p = 0.028) between the diameters of the dermal papillae of the lesional skin areas 0.114 +/- 0.012 mm) and the non-lesional skin areas (0.079 +/- 0.005 mm). Thus, CLSM can be applied for monitoring psoriasis follow-up examinations