Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca\u27s area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance

Rayleigh-Taylor mixing: confinement by stratification and geometry

Rayleigh-Taylor instability has been an area of active research in fluid dynamics for the last twenty years, but relatively little attention has been paid to the dynamics of problems where Rayleigh-Taylor instability plays a role, but is only one component of a more complex system. Here, Rayleigh-Taylor instability between miscible fluids is examined in situations where it is confined by various means: by geometric restriction, by penetration into a stable linear stratification, and by impingement on a stable density interface. Water-based experiments are modelled using a variety of techniques, ranging from simple hand calculation of energy exchange to full three-dimensional numerical simulation. Since there are well known difficulties in modelling unconfined Rayleigh-Taylor instability, the confined test cases have been sequenced to begin with dynamically simple benchmark systems on which existing modelling approaches perform well, then they progress to more complex systems and explore the limitations of the various models. Some work on the phenomenology of turbulent mixing is also presented, including a new experimental technique that allows mixed fluid to be visualised directly, and an analysis of energy transport and mixing efficiency in variable density flows dominated by mixing

Functional pulmonary MRI using hyperpolarised 3He

The microstructure of the lung is complex, containing many branching airways and alveolar sacs for optimal gas exchange. Lung diseases such as cystic fibrosis (CF), asthma, and emphysema lead to a destruction of this microstructure. As such, there is a growing interest in the early identification and assessment of lung disease using non invasive imaging techniques. Pulmonary function tests such as spirometry and plethysmography are currently used for this purpose but can only provide quantitative lung function measurements rather than direct measurements of lung physiology and disease. Computed tomography (CT) has also been used but due to risk of cell damage and mutation from the ionising radiation, long term monitoring of the lungs is severely constrained. Recently, new methods based on magnetic resonance imaging (MRI) have been developed to provide diagnostic imaging of the lung. Conventional MRI is not very well suited for lung imaging due to the very low proton density of the pulmonary airspaces. This problem can be overcome by making the patient inspire noble gases such as 3He whose polarisations have been vastly increased through optical pumping. Therefore 3He MRI permits a non-invasive determination of lung function. The high diffusion coefficient of 3He can be exploited to probe the microstructure of the lung. By measuring how fast 3He diffuses within the lung, the size of the lung microstructure can be assessed. Normally, the airspace walls impede the diffusion of the gas but for diseased lungs where microstructure has been destroyed, diffusion is less restricted and a higher apparent diffusion coefficient (ADC) is observed. The research conducted for this thesis focused on the measurement of ADC using three different MRI pulse sequences with each sequence being designed to assess the peripheral airspaces over different length scales. These sequences were then implemented on three different subject study groups

Functional pulmonary MRI using hyperpolarised 3He

The microstructure of the lung is complex, containing many branching airways and alveolar sacs for optimal gas exchange. Lung diseases such as cystic fibrosis (CF), asthma, and emphysema lead to a destruction of this microstructure. As such, there is a growing interest in the early identification and assessment of lung disease using non invasive imaging techniques. Pulmonary function tests such as spirometry and plethysmography are currently used for this purpose but can only provide quantitative lung function measurements rather than direct measurements of lung physiology and disease. Computed tomography (CT) has also been used but due to risk of cell damage and mutation from the ionising radiation, long term monitoring of the lungs is severely constrained. Recently, new methods based on magnetic resonance imaging (MRI) have been developed to provide diagnostic imaging of the lung. Conventional MRI is not very well suited for lung imaging due to the very low proton density of the pulmonary airspaces. This problem can be overcome by making the patient inspire noble gases such as 3He whose polarisations have been vastly increased through optical pumping. Therefore 3He MRI permits a non-invasive determination of lung function. The high diffusion coefficient of 3He can be exploited to probe the microstructure of the lung. By measuring how fast 3He diffuses within the lung, the size of the lung microstructure can be assessed. Normally, the airspace walls impede the diffusion of the gas but for diseased lungs where microstructure has been destroyed, diffusion is less restricted and a higher apparent diffusion coefficient (ADC) is observed. The research conducted for this thesis focused on the measurement of ADC using three different MRI pulse sequences with each sequence being designed to assess the peripheral airspaces over different length scales. These sequences were then implemented on three different subject study groups

The impact of aerobic exercise on brain's white matter integrity in the Alzheimer's disease and the aging population

The brain is the most complex organ in the body. Currently, its complicated functionality has not been fully understood. However, in the last decades an exponential growth on research publications emerged thanks to the use of in-vivo brain imaging techniques. One of these techniques pioneered for medical use in the early 1970s was known as nuclear magnetic resonance imaging based (now called magnetic resonance imaging [MRI]). Nowadays, the advances of MRI technology not only allowed us to characterize volumetric changes in specific brain structures but now we could identify different patterns of activation (e.g. functional MRI) or changes in structural brain connectivity (e.g. diffusion MRI). One of the benefits of using these techniques is that we could investigate changes that occur in disease-specific cohorts such as in the case of Alzheimer’s disease (AD), a neurodegenerative disease that affects mainly older populations. This disease has been known for over a century and even though great advances in technology and pharmacology have occurred, currently there is no cure for the disease. Hence, in this work I decided to investigate whether aerobic exercise, an emerging alternative method to pharmacological treatments, might provide neuroprotective effects to slow down the evident brain deterioration of AD using novel in-vivo diffusion imaging techniques. Previous reports in animal and human studies have supported these exercise-related neuro-protective mechanisms. Concurrently in AD participants, increased brain volumes have been positively associated with higher cardiorespiratory fitness levels, a direct marker of sustained physical activity and increased exercise. Thus, the goal of this work is to investigate further whether exercise influences the brain using structural connectivity analyses and novel diffusion imaging techniques that go beyond volumetric characterization. The approach I chose to present this work combined two important aspects of the investigation. First, I introduced important concepts based on the neuro-scientific work in relation to Alzheimer’s diseases, in-vivo imaging, and exercise physiology (Chapter 1). Secondly, I tried to describe in simple mathematics the physics of this novel diffusion imaging technique (Chapter 2) and supported a tract-specific diffusion imaging processing methodology (Chapter 3 and 4). Consequently, the later chapters combined both aspects of this investigation in a manuscript format (Chapter 5-8). Finally, I summarized my findings, include recommendations for similar studies, described future work, and stated a final conclusion of this work (Chapter 9)

Research and technology, 1990: Goddard Space Flight Center

Goddard celebrates 1990 as a banner year in space based astronomy. From above the Earth's obscuring atmosphere, four major orbiting observatories examined the heavens at wavelengths that spanned the electromagnetic spectrum. In the infrared and microwave, the Cosmic Background Explorer (COBE), measured the spectrum and angular distribution of the cosmic background radiation to extraordinary precision. In the optical and UV, the Hubble Space Telescope has returned spectacular high resolution images and spectra of a wealth of astronomical objects. The Goddard High Resolution Spectrograph has resolved dozens of UV spectral lines which are as yet unidentified because they have never before been seen in any astronomical spectrum. In x rays, the Roentgen Satellite has begun returning equally spectacular images of high energy objects within our own and other galaxies

Translational Imaging of Pulmonary Gas-Exchange Using Hyperpolarized 129Xe Magnetic Resonance Imaging

<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>Dissertatio

Comparison of sea-ice freeboard distributions from aircraft data and cryosat-2

The only remote sensing technique capable of obtain- ing sea-ice thickness on basin-scale are satellite altime- ter missions, such as the 2010 launched CryoSat-2. It is equipped with a Ku-Band radar altimeter, which mea- sures the height of the ice surface above the sea level. This method requires highly accurate range measure- ments. During the CryoSat Validation Experiment (Cry- oVEx) 2011 in the Lincoln Sea, Cryosat-2 underpasses were accomplished with two aircraft, which carried an airborne laser-scanner, a radar altimeter and an electro- magnetic induction device for direct sea-ice thickness re- trieval. Both aircraft flew in close formation at the same time of a CryoSat-2 overpass. This is a study about the comparison of the sea-ice freeboard and thickness dis- tribution of airborne validation and CryoSat-2 measure- ments within the multi-year sea-ice region of the Lincoln Sea in spring, with respect to the penetration of the Ku- Band signal into the snow