In vivo tissue diagnosis for myocardial infarction using optical spectroscopy with novel spectral interpretation algorithms

In recent decades, the rapid development of optical spectroscopy for tissue diagnosis has been indicative of its high clinical value. The goal of this research is to prove the feasibility of using diffuse reflectance spectroscopy and fluorescence spectroscopy to assess myocardial infarction (MI) in vivo. The proposed optical technique was designed to be an intra-operative guidance tool that can provide useful information about the condition of an infarct for surgeons and researchers. ^ In order to gain insight into the pathophysiological characteristics of an infarct, two novel spectral analysis algorithms were developed to interpret diffuse reflectance spectra. The algorithms were developed based on the unique absorption properties of hemoglobin for the purpose of retrieving regional hemoglobin oxygenation saturation and concentration data in tissue from diffuse reflectance spectra. The algorithms were evaluated and validated using simulated data and actual experimental data. ^ Finally, the hypothesis of the study was validated using a rabbit model of MI. The mechanism by which the MI was induced was the ligation of a major coronary artery of the left ventricle. Three to four weeks after the MI was induced, the extent of myocardial tissue injury and the evolution of the wound healing process were investigated using the proposed spectroscopic methodology as well as histology. The correlations between spectral alterations and histopathological features of the MI were analyzed statistically. ^ The results of this PhD study demonstrate the applicability of the proposed optical methodology for assessing myocardial tissue damage induced by MI in vivo. The results of the spectral analysis suggest that connective tissue proliferation induced by MI significantly alter the characteristics of diffuse reflectance and fluorescence spectra. The magnitudes of the alterations could be quantitatively related to the severity and extensiveness of connective tissue proliferation.^

In vivo characterization of epileptic tissue with optical spectroscopy

For children with intractable seizures, surgical removal of epileptic foci, if identifiable and feasible, can be an effective way to reduce or eliminate seizures. The success of this type of surgery strongly hinges upon the ability to identify and demarcate those epileptic foci. The ultimate goal of this research project is to develop an effective technology for detection of unique in vivo pathophysiological characteristics of epileptic cortex and, subsequently, to use this technology to guide epilepsy surgery intraoperatively. In this PhD dissertation the feasibility of using optical spectroscopy to identify uniquein vivo pathophysiological characteristics of epileptic cortex was evaluated and proven using the data collected from children undergoing epilepsy surgery. ^ In this first in vivo human study, static diffuse reflectance and fluorescence spectra were measured from the epileptic cortex, defined by intraoperative ECoG, and its surrounding tissue from pediatric patients undergoing epilepsy surgery. When feasible, biopsy samples were taken from the investigated sites for the subsequent histological analysis. Using the histological data as the gold standard, spectral data was analyzed with statistical tools. The results of the analysis show that static diffuse reflectance spectroscopy and its combination with static fluorescence spectroscopy can be used to effectively differentiate between epileptic cortex with histopathological abnormalities and normal cortex in vivo with a high degree of accuracy. ^ To maximize the efficiency of optical spectroscopy in detecting and localizing epileptic cortex intraoperatively, the static system was upgraded to investigate histopathological abnormalities deep within the epileptic cortex, as well as to detect unique temporal pathophysiological characteristics of epileptic cortex. Detection of deep abnormalities within the epileptic cortex prompted a redesign of the fiberoptic probe. A mechanical probe holder was also designed and constructed to maintain the probe contact pressure and contact point during the time dependent measurements. The dynamic diffuse reflectance spectroscopy system was used to characterize in vivo pediatric epileptic cortex. The results of the study show that some unique wavelength dependent temporal characteristics (e.g., multiple horizontal bands in the correlation coefficient map γ(λref = 800 nm, λcomp ,t)) can be found in the time dependent recordings of diffuse reflectance spectra from epileptic cortex defined by ECoG.^

In vivo characterization of myocardial tissue post myocardial infarction using combined fluorescence and diffuse reflectance spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region—one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees/severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

In Vivo Characterization of Myocardial Tissue Post Myocardial Infarction Using Combined Fluorescence and Diffuse Reflectance Spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on - (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region - one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees / severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

Functional near infrared spectroscopy study of language, joint attention and motor skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Evaluating the Distribution of Terrestrial Dissolved Organic Matter in a Complex Coastal Ecosystem Using Fluorescence Spectroscopy

The coastal zone of the Florida Keys features the only living coral reef in the continental United States and as such represents a unique regional environmental resource. Anthropogenic pressures combined with climate disturbances such as hurricanes can affect the biogeochemistry of the region and threaten the health of this unique ecosystem. As such, water quality monitoring has historically been implemented in the Florida Keys, and six spatially distinct zones have been identified. In these studies however, dissolved organic matter (DOM) has only been studied as a quantitative parameter, and DOM composition can be a valuable biogeochemical parameter in assessing environmental change in coastal regions. Here we report the first data of its kind on the application of optical properties of DOM, in particular excitation emission matrix fluorescence with parallel factor analysis (EEM-PARAFAC), throughout these six Florida Keys regions in an attempt to assess spatial differences in DOM sources. Our data suggests that while DOM in the Florida Keys can be influenced by distant terrestrial environments such as the Everglades, spatial differences in DOM distribution were also controlled in part by local surface runoff/fringe mangroves, contributions from seasgrass communities, as well as the reefs and waters from the Florida Current. Application of principal component analysis (PCA) of the relative abundance of EEM-PARAFAC components allowed for a clear distinction between the sources of DOM (allochthonous vs. autochthonous), between different autochthonous sources and/or the diagenetic status of DOM, and further clarified contribution of terrestrial DOM in zones where levels of DOM were low in abundance. The combination between EEM-PARAFAC and PCA proved to be ideally suited to discern DOM composition and source differences in coastal zones with complex hydrology and multiple DOM sources.

Funtional Near Infrared Spectroscopy Study of Language, Joint Attention and Motor Skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.