<p>Hyperpolarized (HP) 129Xe MRI has emerged as a viable tool for evaluating lung function without ionizing radiation. HP 129Xe has already been used to image ventilation and quantify ventilation defects. However, this thesis aims to further develop imaging techniques that are capable of imaging, not just ventilation, but also gas transfer within the lung. This ability to image gas transfer directly is enabled by the solubility and chemical shifts of 129Xe that provide separate MR signatures in the airspaces, barrier tissue, and red blood cells (RBCs). </p><p>While 129Xe in the airspace (referred to as gas-phase 129Xe) can be readily imaged with standard vendor-provided imaging sequences, 129Xe in the barrier and RBC compartments (collectively referred to as dissolved-phase 129Xe) has such a rapid T2* (<2 msec at 2T) that even simple gradient recalled echo (GRE) sequences are ineffective at imaging the limited signal before it decays. To minimize these losses from T2* decay, the 3D radial sequence offers much shorter TEs that can image the dissolved-phase 129Xe. Despite their ability to image dissolved-phase signal, however, 3D radial sequences have not yet been widely adopted within the hyperpolarized gas community. In order to demonstrate the potential of the 3D radial pulse sequence, chapter 3 uses standard 129Xe ventilation imaging to compare 3D radial image quality and defect conspicuity with that of the conventional GRE. Since the 3D radial sequence offered comparable performance in ventilation imaging, and also provided the ability to image dissolved-phase 129Xe, chapter 3 establishes that the 3D radial sequence is well-suited for imaging 129Xe in humans.</p><p>Though 3D radial acquisition offers clear advantages for functional 129Xe lung imaging, its non-Cartesian sampling of k-space complicates image reconstruction. Chapter 4 carefully explains the process of gridding-based reconstruction, and describes how problems arising from non-selective RF pulses and undersampling, both of which are commonly employed in hyperpolarized 129Xe imaging, can be avoided by using appropriate reconstruction techniques. Furthermore, we detail a generalized procedure to optimize reconstruction parameters, then demonstrate the benefits of our improved reconstruction methods across both 1H anatomical imaging as well as functional imaging of 129Xe in the gas- and dissolved-phases. </p><p>These dissolved-phase images are particularly interesting because they consist of separate contributions from 129Xe in the RBCs and barrier tissue. Once these two resonances are disentangled from one another, they provide a noninvasive means to measure gas exchange regionally. However, such decomposition of these two resonances is predicated on prior knowledge of their spectroscopic properties. To that end, chapter 5 describes a non-linear spectroscopic curve fitting toolbox that we developed to more accurately characterize the 129Xe spectrum in vivo. Though previously, only two dissolved-phase resonances have ever been described within the lung, our fitting tools were able to identify a third dissolved-phase resonance in both healthy volunteers and healthy controls. Furthermore, we describe several spectroscopic features that differ statistically between our healthy volunteers and IPF subjects to demonstrate that this technique is sensitive to even subtle functional changes within the lung. These spectroscopic measurements provide the basis for imaging gas transfer. </p><p>Describing lung function regionally requires phase-sensitive imaging techniques that can decompose the dissolved-phase signal into images that represent the contribution from the RBC and barrier resonances. To date, only two implementations have been demonstrated, and both suffered from poor SNR and challenges in quantifying gas transfer. Chapter 6 adds quantitative processing techniques that improve phase sensitive imaging of 129Xe gas transfer. These methods 1) normalize both the RBC and barrier uptake images by gas-phase magnetization so that intensities can be compared across subjects, 2) compress the dynamic range of these functional images to enhance their perceived SNR, and 3) derive colormap thresholds from a healthy reference population to give intensities meaningful context.</p><p>To show the value of our quantitative gas transfer imaging, chapter 7 applies these techniques to a cohort of healthy volunteers and another of IPF patients. Since patients with IPF exhibit a progressive thickening and hardening of the pulmonary interstitium that severely restricts the transport of gases between the lungs and blood, they represent an ideal population to prove out our methods. This analysis identifies several patterns to the RBC and barrier distributions which could potentially represent different stages of disease. Furthermore, we demonstrate that our MRI-based findings correlate well with DLCO and FVC, and to a lesser extent with the structural cues seen in CT. This suggests that 129Xe imaging offers complimentary functional information that can’t be derived from CT, while also describing its spatial distribution unlike PFTs. </p><p>The work in this thesis has transitioned our HP 129Xe gas transfer studies from a proof of concept to an optimized and quantitative imaging protocol with robust processing pipelines. Using these MRI methods, we have shown that we can directly and quantitatively probe pulmonary ventilation and gas transfer within a single breath hold. In IPF, such noninvasive imaging methods are desperately needed to monitor the efficacy of these new treatments to ensure that the associated medical expense is justified with positive changes in outcomes. Finally, these new functional contrasts will be useful in studying other cardiopulmonary diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension.</p> / Dissertation

Thesis (M.S.)--Ohio State University, 2009. / Title from first page of PDF file. Includes vita. Includes bibliographical references (p. xv-130).

Atmospheric transport and air-water exchange of organochlorine pesticides (OCPs) were investigated in temperate North America and the Arctic. OCPs studied were hexachlorocyclohexanes (HCHs, a-, b- and g-isomers), components of technical chlordane (trans- and cis-chlordane, trans-nonachlor), dieldrin, heptachlor exo-epoxide and toxaphene. Air and water samples were taken on cruises in the Great Lakes and Arctic to determine concentrations and gas exchange flux direction and magnitude. The Henry’s law constant, which describes the equilibrium distribution of a chemical between air and water, was determined for several OCPs as a function of temperature and used to assess the net direction of air-water exchange. Air samples were collected in Alabama to investigate southern U.S. sources of OCPs. Chemical markers (isomers, and enantiomers of chiral OCPs) were employed to infer sources and trace gas exchange. Elevated air concentrations of toxaphene and chlordanes were found in Alabama relative to the Great Lakes, indicating a southern U.S. source. Profiles of toxaphene compounds in air were similar to those in soil by being depleted in easily degraded species, suggesting that soil emissions control air concentrations. Gas exchange fluxes in the Great Lakes indicated near-equilibrium between air and water with excursions to net volatilization or deposition. Net volatilization of a-HCH from the Arctic Ocean was traced by evasion of non-racemic a-HCH into the atmosphere.

Thesis (M.S.)--Springfield College, 2002. / Includes bibliographical references.

Intrapulmonary arteriovenous anastomoses (IPAVA) have been known to exist as part of the normal pulmonary vasculature for over 50 years but have been underappreciated by physiologists and clinicians. Using a technique called saline contrast echocardiography we and others have demonstrated that during exercise or when breathing low oxygen gas mixtures IPAVA open, but breathing 100% oxygen during exercise prevents them from opening. However, the mechanism(s) for this dynamic regulation and the role IPAVA play in affecting pulmonary gas exchange efficiency remain unknown. In Chapter IV the infusion of epinephrine and dopamine into resting subjects opened IPAVA. While it is possible this opening was due to the direct vasoactive action of these catecholamines, the opening may simply be due to increases in cardiac output and pulmonary artery systolic pressure secondary to the cardiac effects of these drugs. In Chapter V I used Technetium-99m labeled macroaggregated albumin (99mTc-MAA) to quantify blood flow through IPAVA in exercising healthy humans. Initial attempts to correct for attenuation of the emitted signal were unsuccessful due to the time necessary for data acquisition and the resulting accumulation of free-99mTc. However, I used a blood sample to calculate freely circulating 99mTc which could be subtracted from the shunt fraction. Using this procedure I demonstrated for the first time using filtered solid particles that breathing 100% oxygen reduces blood flow through IPAVA during exercise. Finally, in Chapter VI I tackled the elephant in the room surrounding IPAVA in healthy humans: do these vessels play a role in pulmonary gas exchange efficiency? Our data suggest that the efficiency of pulmonary gas exchange is dependent on the driving pressure gradient for oxygen and the distance to blood flowing through the core of IPAVA. As such, with increases in exercise intensity the diffusion distance and transit time of blood at the core of IPAVA prevent complete gas exchange, thus blood flow through IPAVA acts as a shunt. This dissertation includes previously unpublished co-authored material.

Rhododendron maximum L. is a dominant subcanopy species in the southern Appalachian Mountains. R. maximum undergo distinct thermonastic leaf movements (TLM). The purpose of these movements has not yet been determined. Previous studies have suggested TLM are a photoprotective mechanism for the dynamic light environment of the subcanopy in a deciduous forest during winter. The present study aimed to determine the effects of restricting TLM on photoinhibition, net photosynthesis, and other gas exchange parameters, particularly during the early spring. After restricting TLM on certain leaves, we observed the above parameters from autumn 2005 to late spring 2006. Our results indicated that photoinhibition increased (lower Fv/Fm) in treatment leaves over reference leaves throughout the winter. The difference became greater during the early spring, when reference leaves began to return to normal levels of photochemical efficiency and treatment leaves sustained low Fv/Fm. Net photosynthesis was lower for treatment leaves than reference leaves. This became most significant during the early spring, when maximum carbon gain is possible. Finally, gas exchange parameters as measured by light and CO2 response curves did not indicate any significant difference between treatment and reference leaves post canopy closure. Out results suggest that TLM are an important mechanism for photoprotection, allowing leaves of R. maximum to recover quickly during the early spring and maximize their early spring carbon gain. / Master of Science

<p>The diagnosis and treatment of pulmonary diseases still rely on pulmonary function tests that offer archaic or insensitive biomarkers of lung structure and function. As a consequence, chronic obstructive pulmonary disease is the third leading cause of death in the US, and the hospitalization costs for asthma are on the order of $29 Billion. Pulmonary diseases have created a large and unsustainable economic burden, and hence there is still a dire need for biomarkers that can predict early changes in lung function. The work presented in this thesis looks to address this very issue, by taking advantage of the unique properties of hyperpolarized (HP) <super>129</super>Xe in conjunction with magnetic resonance imaging (MRI), to probe the fundamental function of the lung - gas-exchange. </p><p>While a bulk of the inhaled HP <super>129</super>Xe stays in the alveolar spaces, its moderate solubility in the pulmonary tissues causes a small fraction of this xenon in the alveolar spaces to diffuse into the pulmonary barrier tissue and plasma, and further into the red blood cells (RBC). Additionally, when in either of these compartments, xenon experiences a unique shift in its resonance frequency from the gas-phase (barrier - 198 ppm, RBC - 217 ppm). These unique resonances are collectively called the dissolved-phase of xenon. As the pathway taken by xenon to reach the RBCs is identical to that of oxygen, this dissolved-phase offers a non-invasive probe to study the oxygen transfer pathway, and imaging its distribution, to first order, would give us an image of gas-exchange in the lung.</p><p>Gas-exchange is controlled by ventilation, perfusion, and lastly diffusion of gases across the capillary membrane. This process of diffusion is dictated by Fick's first law of diffusion, and hence the volume of gas taken up by the capillary blood stream depends on the alveolar surface area, and the interstitial thickness. Interestingly, changes in these factors can be measured using the resonances of xenon. Changes in the alveolar surface area brought on by diseases like emphysema will increase the diffusion of xenon within the alveolus. Thus, by using diffusion-weighted imaging of the gas-phase of <super>129</super>Xe, which is the focus of chapter 3, one can extract the `apparent diffusion coefficient' (ADC) of xenon, that is sensitive to the changes in the alveolar surface area. The dissolved-phase on the other hand, while sensitive to the surface area, is also sensitive to subtle changes in the interstitial thickness. In fact, after the application of an RF pulse on the dissolved-phase, the recovery time for the xenon signal in the RBCs is significantly delayed by micron scale thickening of the interstitium. This delayed signal recovery can be used as a sensitive marker for diffusion impairment in the lung. </p><p>While direct imaging of the dissolved-phase was shown to be feasible, truly quantifying gas-exchange in the lung will require two additional technical advances - 1) As the gas-phase is the source magnetization for the dissolved-phase signal, it is imperative to acquire both the gas and dissolved-phase images in a single breath. The technical details of this achievement are discussed in chapters 4 and 5. 2) As the dissolved-phase consists of both the barrier and the RBC components, obtaining a fundamental image of gas-exchange in the lung will require creating independent images of <super>129</super>Xe in the barrier and <super>129</super>Xe in the RBCs. This goal first required creating a global metric of gas-transfer in the lung (chapter 6), which aided the implementation of the 1-point Dixon acquisition strategy to separate the components of the dissolved-phase. In conjunction with aim 1, it was finally possible to image all three resonances of <super>129</super>Xe in a single breath (chapter 7). These <super>129</super>Xe-RBC images were acquired in healthy volunteers and their efficacy was tested in subjects with idiopathic pulmonary fibrosis (IPF). These IPF subjects are known for their characteristic diffusion limitation, and in regions of fibrosis shown on their CT scans, the <super>129</super>Xe-RBC images showed gas-transfer defects. </p><p>Hyperpolarized <super>129</super>Xe MRI thus provides a non-invasive, ionizing radiation free method to probe ventilation, microstructural changes and most importantly, gas-exchange. These preliminary results indicate that xenon MRI has potential as a sensitive tool in therapeutic clinical trials to evaluate longitudinal changes in lung function.</p> / Dissertation

Methane (CH4) and carbon dioxide (CO2) are two important greenhouse gases. Recent studies have shown that lakes, although they cover a small area of the globe, can be very important natural sources of atmospheric CH4 and CO2. It is therefore important to monitor the fluxes of these gases between lakes and the atmosphere in order to understand the processes that govern the exchange. By using the eddy covariance method for lake flux studies, the resolution in time and in space of the fluxes is increased, which gives more information on the governing processes. Eddy covariance measurements at a Swedish lake revealed a diel cycle in the fluxes of both CH4 and CO2, with higher fluxes during nighttime than daytime. The high nighttime CO2 fluxes could to a large extent be explained with enhanced transfer velocities due to waterside convection. For the diel cycle of CH4 flux it was suggested that waterside convection could enhance the transfer velocity, transport CH4 rich water to the surface, as well as trigger ebullition. Simultaneous flux measurements of CH4 and CO2 have been presented using both the eddy covariance method and the floating chambers method of which the latter is the traditional measuring method for lake fluxes. For CO2 the two methods agreed well during some periods but differed considerably during others. Disagreement between the methods might be due to horizontal heterogeneity in partial pressure of CO2 in the lake. The methods agreed better for the CH4 flux measurements. However, it is clear that due to the discontinuous nature of the floating chambers, this method will likely miss important high flux events. The main conclusions of this thesis are: 1) the two gas flux methods are not directly comparable and should be seen as supplementary to each other 2) waterside convection enhances the fluxes of both CH4 and CO2 over the water-air surface. If gas flux measurements are not conducted during nighttime, potential high flux periods might be missed and estimates of the total amount of gas released from lakes to the atmosphere may be biased.

Le travail présenté dans ce manuscrit décrit quelques-uns des mécanismes qui régissent les échanges de CO2 et d’eau dans le mésophylle. Nous présentons dans une première partie une méthode originale qui utilise une technique de traçage isotopique et une modélisation deséchanges gazeux pour décrire le transfert du CO2 et la concentration de CO2 aux sites catalytiques des anhydrases carboniques. Dans une deuxième partie, cette approche nous permet de caractériser la diffusion de CO2 intra-mésophylienne et d’aborder l’étude du rôle des anhydrases carboniques et des aquaporines dans la facilitation du transport de CO2. Cette étude est basée sur une analyse fonctionnelle de mutants d’insertions d’Arabidopsis affectésdans l’expression des anhydrases carboniques (ACs) ou des aquaporines. La contribution fonctionnelle d’une AC, bCA4 localisée à la membrane plasmique et récemment identifiée estanalysée plus spécifiquement. Dans une troisième partie, nous montrons par un travail de modélisation que l’approche de traçage isotopique précédemment introduite pour étudier le transfert de CO2 peut être utilisée pour étudier la compartimentation de l’eau mésophyllienne et les flux associés. Cette approche nous permet de démontrer l’existence d’une compartimentation fonctionnelle de l’eau foliaire. La signification de cette compartimentation est discutée, et une nouvelle méthode de suivi quantitatif des flux d’eau entre l’apoplasme etle symplasme est proposée. Enfin, dans une dernière partie nous abordons expérimentalement les effets de l’acide abscissique sur la transpiration foliaire et la régulation stomatique. / N this study, mechanisms that govern CO2 and water fluxes in the mesophyll are investigated. In a first part, an original approach based on isotopic tracing and modeling of gas exchange is presented to describe the CO2 transfer towards sites of carbonic anhydrases catalysis that are used to probe the intracellular CO2 concentration. In a second part, this approach allows to characterize the intracellular diffusion of CO2 and to address the implication of carbonicanhydrases and aquaporins in the facilitation of the CO2 transfer. The functional analysis is based on the characterization of Arabidopsis mutants in which the expression of some carbonic anhydrases (CAs) or aquaporins is impaired. The implication of a recently identified CA, bCA4 located at the plasma membrane, is studied in detail. In a third part a modeling approach is used to show that the method of isotopic tracing introduced to probe the CO2 fluxes can also be used to study the compartmentation of the mesophyll water and the associated fluxes. The basis of this functional compartmentation is analyzed and a newmethod is proposed to quantitatively monitor the water fluxes between the apoplasm and the symplasm. In a last part, the effects of abscissic acid on the leaf transpiration and on the stomatal aperture regulation are addressed.

Aquatic ecosystems play a substantial role in global cycling of carbon (C), despite covering only about 4% of the earth surface. They emit large amounts of greenhouse gases (GHG) to the atmosphere, comparable to the amount of C stored annually in terrestrial ecosystems. In addition, C can be buried in lake sediments. Headwater systems are located at the interface of the terrestrial and aquatic environment, and are first in line to process terrestrial C and throughout its journey through the aquatic continuum. The uncertainties in global estimates of aquatic GHG emissions are largely related to these headwater systems, as they are highly variable in time and space, and underrepresented in global assessments. The overall aim of this thesis was therefore to study GHG exchange between sediment, water and air in headwater systems, from both an ecosystem perspective and at the small scale of physical drivers of gas exchange. This thesis demonstrates that carbon dioxide (CO2) emission from headwater systems, especially streams, was the main pathway of C loss from surface waters from a lake catchment. Of the total aquatic CO2-emission of the catchment, 65% originated from stream systems that covered only 0.1% of the total catchment area. The gas transfer velocity (k) was the main driver of stream CO2-emission, but there was a high variability in k on small spatial scales (meters). This variability may have implications for upscaling GHG emissions, especially when using scaled k estimates. Lake sediments only contributed 16% to total lake C emission, but in reality, sediment C emission is probably even lower because experimentally determined sediment C flux returns high estimates that are biased since artificially induced turbulence enhances C flux rates beyond in-situ conditions. When sediment C flux is estimated in-situ, in natural bottom water turbulence conditions, flux rates were lower than those estimated experimentally. Conclusively, this thesis shows that GHG emissions from small aquatic ecosystems are dominant over other aquatic C fluxes and that our current knowledge regarding the physical processes controlling gas exchange from different small aquatic systems is limited, implying an inherent uncertainty of GHG emission estimates from small aquatic ecosystems.