Diffusion weighted imaging (DWI) and dynamic susceptibility contrast-enhanced (DSC) perfusion-weighted imaging (PWI) are commonly employed in clinical practice and in research to give pathophysiological information for patients with acute ischemic stroke. DWI is thought to roughly reflect the severely damaged infarct core, while DSC-PWI reflects the area of hypoperfusion. The volumetric difference between DWI and DSC-PWI is termed the PWI/DWI-mismatch, and has been suggested as an MRI surrogate of the ischemic penumbra. However, due to the application of a contrast agent, which has potentially severe side-effects (e.g., nephrogenic systemic fibrosis), the DSC-PWI precludes repetitive examinations for monitoring purposes. New approaches are being sought to overcome this shortcoming. BOLD (blood oxygen-level dependent) signal can reflect the metabolism of blood oxygen in the brain and hemodynamics can be assessed with resting-state fMRI. The aim of this thesis was to use resting-state fMRI as a new approach to give similar information as DSC-PWI. This thesis comprises two studies: In the first study (see Chapter 2), two resting-state fMRI methods, local methods which compare low frequency amplitudes between two hemispheres and a k-means clustering approach, were applied to investigate the functional damage of patients with acute ischemic stroke both in the time domain and frequency domain. We found that the lesion areas had lower amplitudes than contralateral homotopic healthy tissues. We also differentiated the lesion areas from healthy tissues using a k-means clustering approach. In the second study (see Chapter 3), time-shift analysis (TSA), which assesses time delays of the spontaneous low frequency fluctuations of the resting-state BOLD signal, was applied to give similar pathophysiological information as DSC-PWI in the acute phase of stroke. We found that areas which showed a pronounced time delay to the respective mean time course were very similar to the hypoperfusion area. In summary, we suggest that the resting-state fMRI methods, especially the time-shift analysis (TSA), may provide comparable information to DSC-PWI and thus serve as a useful diagnostic tool for stroke MRI without the need for the application of a contrast agent.

No description available.

Cerebral ischemia is a vascular disorder that is characterized by the reduction of blood supply to the brain, resulting in impaired metabolism and finally death of brain cells. Cerebral ischemia is a major clinical problem associated with global morbidity and mortality rates of about 30%. Clinical management of cerebral ischemia relies heavily on perfusion analysis using dynamic susceptibility contrast MRI (DSC-MRI). DSC-MRI analysis is performed using mathematical models that simulate the underlying vascular physiology of brain. Cerebral perfusion is calculated using perfusion imaging and is used as a marker of tissue health status; low perfusion being an indicator of impaired tissue metabolism. In addition to measurement of cerebral perfusion, it is possible to quantify the blood flow variation within the capillary network referred to as cerebral microvascular hemodynamics. It has been hypothesized that microvascular hemodynamics are closely associated with tissue oxygenation and that hemodynamics might undergo a considerable amount of variation to maintain normal tissue metabolism under conditions of ischemic stress. However with DSC-MRI perfusion imaging, quantification of cerebral hemodynamics still remains a big challenge. Singular Value Decomposition (SVD) is currently a standard methodology for estimation of cerebral perfusion with DSC-MRI in both research and clinical settings. It is a robust technique for quantification of cerebral perfusion, however, the quantification of hemodynamic information cannot be achieved with SVD methods because of the non-physiological behaviour of SVD in microvascular hemodynamic estimation. SVD is sensitive to the noise in the MR signal which appears in the calculated microvascular hemodynamics, thus making it difficult to interpret for pathophysiological significance. Other methods, including model-based approaches or methods based on likelihood estimation, stochastic modeling and Gaussian processes, have been proposed. However, none of these have become established as a means to study tissue hemodynamics in perfusion imaging. Possibly because of the associated constrains in these methodologies that limited their sensitivity to hemodynamic variation in vivo. The objective of the research presented in this thesis is to develop and to evaluate a method to perform a quantitative estimation of cerebral hemodynamics using DSC-MRI. A new Control Point Interpolation (CPI) method has been developed to perform a non-parametric analysis for DSC-MRI. The CPI method was found to be more accurate in estimation of cerebral perfusion than the alternative methods. Capillary hemodynamics were calculated by estimating the transit time distribution of the tissue capillary network using the CPI method. The variations in transit time distribution showed quantitative differences between normal tissue and tissue under ischemic stress. The method has been corrected for the effects of macrovascular bolus dispersion and tested over a larger clinical cohort of patients with atherosclerosis. CPI method is thus a promising method for quantifying cerebral hemodynamics using perfusion imaging. CPI method is an attempt to evaluate the use of quantitative hemodynamic information in diagnostic and prognostic monitoring of patients with ischemia and vascular diseases.

L'étude des excitations magnétiques de faible amplitude existant dans des films minces à aimantation non uniforme dans la gamme des hautes fréquences, typiquement entre quelques dizaines de MHz et quelques dizaines de GHz, constitue le sujet de ce mémoire. Le cas idéal de films magnétiques possédant une anisotropie perpendiculaire et présentant une configuration d'équilibre de l'aimantation sous forme de rubans parallèles et périodiques est étudié en détail. Dans le cas de films à forte anisotropie perpendiculaire, les spectres théoriques de susceptibilité dynamique calculés à l'aide de modèles analytiques puis, à partir de simulations numériques 2D de micromagnétisme dynamique, font apparaître des excitations localisées soit à l'intérieur des domaines magnétiques soit à l'intérieur des parois magnétiques. Ces résultats ont été comparés de façon satisfaisante avec des résultats expérimentaux issus de mesures de résonance ferromagnétique réalisées sur des films monocristallins de grenats ferrimagnétiques. Toutefois, les largeurs de raie expérimentales associées aux excitations de parois excèdent celles calculées en utilisant le terme dissipatif de Gilbert. Dans le cas de films à faible anisotropie perpendiculaire, les spectres théoriques de susceptibilité dynamique présentent de multiples excitations magnétiques liées à la forte hétérogénéité des configurations d'équilibre de l'aimantation de type rubans faibles. Les analyses modales effectuées à partir des simulations micromagnétiques dynamiques indiquent l'existence de modes de surface et de volume localisés dans différentes régions de spins à l'intérieur du film. L'influence de différents paramètres (anisotropie perpendiculaire, épaisseur du film, champ magnétique statique) sur les principales caractéristiques des spectres (nombre de résonances, fréquences de résonance, intensités et largeurs de raie) est ensuite étudiée. Ces simulations micromagnétiques dynamiques permettent d'interpréter des spectres expérimentaux complexes de perméabilité dynamique mesurés sur des films ferromagnétiques amorphes. Quelques perspectives concernant la dynamique de l'aimantation de faible amplitude dans différents objets magnétiques sont ensuite présentées.

Diffusion weighted imaging (DWI) and dynamic susceptibility contrast-enhanced (DSC) perfusion-weighted imaging (PWI) are commonly employed in clinical practice and in research to give pathophysiological information for patients with acute ischemic stroke. DWI is thought to roughly reflect the severely damaged infarct core, while DSC-PWI reflects the area of hypoperfusion. The volumetric difference between DWI and DSC-PWI is termed the PWI/DWI-mismatch, and has been suggested as an MRI surrogate of the ischemic penumbra. However, due to the application of a contrast agent, which has potentially severe side-effects (e.g., nephrogenic systemic fibrosis), the DSC-PWI precludes repetitive examinations for monitoring purposes. New approaches are being sought to overcome this shortcoming. BOLD (blood oxygen-level dependent) signal can reflect the metabolism of blood oxygen in the brain and hemodynamics can be assessed with resting-state fMRI. The aim of this thesis was to use resting-state fMRI as a new approach to give similar information as DSC-PWI. This thesis comprises two studies: In the first study (see Chapter 2), two resting-state fMRI methods, local methods which compare low frequency amplitudes between two hemispheres and a k-means clustering approach, were applied to investigate the functional damage of patients with acute ischemic stroke both in the time domain and frequency domain. We found that the lesion areas had lower amplitudes than contralateral homotopic healthy tissues. We also differentiated the lesion areas from healthy tissues using a k-means clustering approach. In the second study (see Chapter 3), time-shift analysis (TSA), which assesses time delays of the spontaneous low frequency fluctuations of the resting-state BOLD signal, was applied to give similar pathophysiological information as DSC-PWI in the acute phase of stroke. We found that areas which showed a pronounced time delay to the respective mean time course were very similar to the hypoperfusion area. In summary, we suggest that the resting-state fMRI methods, especially the time-shift analysis (TSA), may provide comparable information to DSC-PWI and thus serve as a useful diagnostic tool for stroke MRI without the need for the application of a contrast agent.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19403号 / 医博第4054号 / 新制||医||1012(附属図書館) / 32428 / 京都大学大学院医学研究科医学専攻 / (主査)教授 前川 平, 教授 平岡 眞寛, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

В работе изучается динамическая восприимчивость феррожидкости, которая моделируется системой взаимодействующих подвижных магнитных частиц. Предполагается, что система находится в постоянном и переменном магнитном полях, направленных параллельно друг другу. / In this work, we study the dynamic susceptibility of a ferrofluid, which is modeled by an system of interacting moving magnetic particles. It is assumed that the system is in a constant and an alternating magnetic field, directed parallel to each other.

В работе реализован численный алгоритм для решения уравнения Фоккера-Планка, позволяющий получать значения первой и третьей гармоники ансамбля взаимодействующих частиц для различных амплитуд переменного поля. В формулы первой и третьей гармоники вводились функции, зависящие от параметра и восприимчивости Ланжевена, с неопределенными коэффициентами. Неопределенные коэффициенты находились методом наименьших квадратов. Выражения для функций приближались данными из численного решения уравнения Фоккера-Планка и затем минимизировались относительно неопределённых коэффициентов. Получившиеся формулы сравнивались с численным решением и с известными теориями. / In this work, a numerical algorithm for solving the Fokker-Planck equation, which allows to obtain the values of the first and third harmonics of the ensemble of interacting particles for different amplitudes of the alternating field, was implemented. The functions depending on the parameter and Langevin susceptibility with uncertain coefficients were introduced into the formulas for the first and third harmonics. The uncertain coefficients were found by the least-squares method. Expressions for the functions were approximated with data from the numerical solution of the Fokker-Planck equation and then minimized with respect to the uncertain coefficients. The resulting formulas were compared with the numerical solution and with known theories.

<p>    </p> <p>Cerebrovascular diseases, such as stroke, constitute the most common life-threatening neurological disease in the United States. To support normal brain function, maintaining adequate brain perfusion (i.e., cerebral blood flow (CBF)) is important. Therefore, it is crucial to assess the brain perfusion so that early intervention in cerebrovascular diseases can be applied if abnormal perfusion is observed. The goal of my study is to develop metrics to measure the brain perfusion through modeling brain physiology using resting-state and task-based blood-oxygenation-level- dependent (BOLD) functional MRI (fMRI). My first and second chapters focused on deriving the blood arrival time using the resting-state BOLD signal. In the first chapters, we extracted the systemic low-frequency oscillations (sLFOs) in the fMRI signal from the internal carotid arteries (ICA) and the superior sagittal sinus (SSS). Consistent and robust results were obtained across 400 scans showing the ICA signals leading the SSS signals by about 5 seconds. This delay time could be considered as an effective perfusion biomarker that is associate with the cerebral circulation time (CCT). To further explore sLFOs in assessing dynamic blood flow changes during the scan, in my second chapter, a “carpet plot” (a 2-dimensional plot time vs. voxel) of scaled fMRI signal intensity was reconstructed and paired with a developed slope-detection algorithm. Tilted vertical edges across which a sudden signal intensity change took place were successfully detected by the algorithm and the averaged propagation time derived from the carpet plot matches the cerebral circulation time. Given that CO₂ is a vasodilator, controlling of inhaled CO₂ is able to modulate the BOLD signal, therefore, as a follow-up study, we focused on investigating the feasibility of using a CO₂ modulated sLFO signal as a “natural” bolus to track CBF with the tool developed from the second chapter. Meaningful transit times were derived from the CO₂-MRI carpet plots. Not only the timing, the BOLD signal deformation (the waveform change) under CO₂ challenge also reveals very useful perfusion information, representing how the brain react to stimulus. Therefore, my fourth chapter focused on characterizing the brain reaction to the CO₂ stimulus to better measure the brain health using BOLD fMRI. Overall, these studies deepen our understanding of fMRI signal and the derived perfusion parameters can potentially be used to assess some cerebrovascular diseases, such as stroke, ischemic brain damage, and steno-occlusive arterial disease in addition to functional activations. </p>

В данной работе, основываясь на решении уравнения Фоккера-Планка-Брауна аналитически определена динамическая магнитная восприимчивость обездвиженных магнитных частиц к слабым переменным магнитным полям с учетом межчастичных диполь-дипольных взаимодействий. Полученное решение, а также известные из литературы аналитические и численные данные динамической восприимчивости систем подвижных и обездвиженных взаимодействующих магнитных частиц использовались для моделирования и анализа удельной поглощаемой мощности в зависимости от режимных параметров рассматриваемой системы. / In that work, based on the solution of the Fokker-Planck-Brown equation, the dynamic magnetic susceptibility of immobilized magnetic particles to weak alternating magnetic fields is analytically determined taking into account interparticle dipole-dipole interactions. The solution obtained, as well as the analytical and numerical data of the dynamic susceptibility of systems of moving and immobilized interacting magnetic particles known from the literature, were used to model and analyze the specific loss power depending on the regime parameters of the system under consideration.