Time resolved magneto-optical measurements of ultrafast demagnetization dynamics

In 1996 a paper by Beaurepaire et al. [PRL, 1996] reported on an ultrafast magneto-optic investigation on Nickel. It showed an ultrafast reduction of magnetization within the first picoseconds and a subsequent recovery on a slower time scale. This was the first evidence of an all-optical magnetization reduction on a femtosecond time scale initiating great interest of the scientific community. Since then, theoretical and experimental efforts have been made to understand what lies at the basis of optical ultrafast demagnetization. The great complexity arises from the required transfer of energy and angular momentum between non-equilibrium electronic, spin and lattice degrees of freedom on a femtosecond time scale. The most successful theory developed in the last decade [Koopmans et al., J. Magn. Magn. Mat., 2005] assumes the lattice as an angular momentum reservoir through the Elliott-Yafet spin flip scattering. After optical excitation of the electronic system, a finite spin flip probability asf is attributed to each electron-phonon scattering event. However, literature on theoretical calculations of asf disagrees, whether this effect alone is sufficient to explain the magnitude of experimentally observed ultrafast demagnetization, or not. In 2010 Battiato et al. [PRL, 2010] proposed a model based on superdiffusive spin transport as a mechanism for ultrafast demagnetization. Optically excited, non equilibrium (NEQ) electrons have a spin dependent velocity and lifetime, hence leading to significant spin-currents. Majority spins have a larger mobility than minority spins, causing a depletion of majority spins in the (probed) magnetic layer, therefore reducing the magnetization. In addition to fundamental issues, there are strong interests in possible technology applica- tions, since magnetic materials are employed in magnetic data storage. The quest of technology progress is for a smaller bit area and for a faster writing process. For this reason it is of great interest to understand the limiting time scales in which the magnetic order can be manipulated and develop new techniques for this purpose. The availability of laser sources with short pulses with a temporal width of tens or few hundreds of femtoseconds allows studying sub-picosecond dynamics with the so called pump and probe technique. A short pump pulse triggers the ultrafast dynamics, while a short probe pulse allows studying the induced non-equilibrium effects. This kind of investigation can be extended to magnetic materials taking advantage of the magneto-optical Kerr effect (MOKE). MOKE refers to the change in the state of polarization when polarized light is reflected off a magnetized material. Detecting this change allows measuring the magnetization of a sample. My thesis work was done at the Technische Universitaet Berlin, where a time resolved MOKE (TR-MOKE) experimental set up is available. I started my work by implementing important improvements of the setup, among others they included testing and installation of a new pho- todetector and optimization of the micro-focusing of the pump and probe pulses at the sample surface. The TR-MOKE set up allows acquiring demagnetization curves from thin samples, which are then analysed to infer the demagnetization and re-magnetization time constants. Since, at the moment, there is no generally accepted model to describe demagnetization curves, several different approaches are found in literature. It was thus necessary to discuss each of them and check whether fitting results depend on the model used. This was actually the case and one model was chosen to analyse all data of this thesis, in order to compare results from different samples. The samples investigated were specifically designed to test the role of spin superdiffusion. Gold gratings with nanometre dimension were structured onto the surface of a magnetic Co/Pt multilayer (ML), leading to nanometre spatially modulated excitation patterns. Light impinging directly on the gold stripes is absorbed, while the magnetic material between gold stripes is excited. There is thus a lateral temperature gradient which favours spin superdiffusion. Indeed a faster demagnetization is found in samples featuring the gold nanostructures compared to the flat surface. Due to the geometry of the structures and to interface effects, the excitation intensity is locally enhanced and this effect is visible in the remagnetization time of the structured sample compared to the film. Quantification of this enhancement confirms the theoretical expectations. In addition, ultrafast demagnetization processes in thin magnetic Co/Pt ML grown on dif- ferent substrates was analysed. Strikingly, we find no significant difference in the magnitude of the demagnetization, for films grown on conducting or insulating substrates. This is a clear indication that superdiffusive spin transport alone cannot explain the phenomenon of ultrafast demagnetization, because all diffusion phenomena are inhibited for an insulating substrate. In the present days, theoretical and experimental ultrafast magnetism face the challenge to develop a model where the spin flip scattering and the spin superdiffusion coexist as microscopic mechanisms for ultrafast demagnetization. This work is a part of this effort and experimental evidences are analysed taking into account both of these microscopic models

Cerebral vasoreactivity in response to a headof-bed position change is altered in patients with moderate and severe obstructive sleep apnea

Obstructive sleep apnea (OSA) can impair cerebral vasoreactivity and is associated with an increased risk of cerebrovascular disease. Unfortunately, an easy-to-use, non-invasive, portable monitor of cerebral vasoreactivity does not exist. Therefore, we have evaluated the use of near-infrared diffuse correlation spectroscopy to measure the microvascular cerebral blood flow (CBF) response to a mild head-of-bed position change as a biomarker for the evaluation of cerebral vasoreactivity alteration due to chronic OSA. Furthermore, we have monitored the effect of two years of continuous positive airway pressure (CPAP) treatment on the cerebral vasoreactivity.Peer ReviewedPostprint (published version

Is hypogammaglobulinemia a constant feature in Good's syndrome?

Thymomas are rare tumors, which can be associated to a variety of paraneoplastic syndromes, including a fatal hypogammaglobulinemia, namely Good's Syndrome (GS). Although the combination of thymoma and hypogammaglobulinemia is regarded as sufficient for diagnosis of Good's syndrome, some thymoma patients with a clear clinical picture of immunodeficiency present normal levels of immunoglobulins. We describe the case of a patient, with a 20-year history of thymoma, who underwent several operations and lines of chemotherapy, and suffered from recurrent infections, including one rare skin infection from Pseudoallescheria boydii. The patient constantly presented normal levels of gammaglobulins

Cerebral oxygenation and blood flow in normal term infants at rest measured by a hybrid near-infrared device (BabyLux)

Peer ReviewedPostprint (author's final draft

Cerebral vasoreactivity in response to a head-of-bed position change is altered in patients with moderate and severe obstructive sleep apnea

Obstructive sleep apnea (OSA) can impair cerebral vasoreactivity and is associated with an increased risk of cerebrovascular disease. Unfortunately, an easy-to-use, non-invasive, portable monitor of cerebral vasoreactivity does not exist. Therefore, we have evaluated the use of near-infrared diffuse correlation spectroscopy to measure the microvascular cerebral blood flow (CBF) response to a mild head-of-bed position change as a biomarker for the evaluation of cerebral vasoreactivity alteration due to chronic OSA. Furthermore, we have monitored the effect of two years of continuous positive airway pressure (CPAP) treatment on the cerebral vasoreactivity. CBF was measured at different head-of-bed position changes (supine to 30° to supine) in sixty-eight patients with OSA grouped according to severity (forty moderate to severe, twenty-eight mild) and in fourteen control subjects without OSA. A subgroup (n = 13) with severe OSA was measured again after two years of CPAP treatment. All patients and controls showed a similar CBF response after changing position from supine to 30° (p = 0.819), with a median (confidence interval) change of -17.5 (-10.3, -22.9)%. However, when being tilted back to the supine position, while the control group (p = 0.091) and the mild patients with OSA (p = 0.227) recovered to the initial baseline, patients with moderate and severe OSA did not recover to the baseline (9.8 (0.8,12.9)%, p < 0.001) suggesting altered cerebral vasoreactivity. This alteration was correlated with OSA severity defined by the apnea-hypopnea index, and with mean nocturnal arterial oxygen saturation. The CBF response was normalized after two years of CPAP treatment upon follow-up measurements. In conclusion, microvascular CBF response to a head-of-bed challenge measured by diffuse correlation spectroscopy suggests that moderate and severe patients with OSA have altered cerebral vasoreactivity related to OSA severity. This may normalize after two years of CPAP treatment

Concurrent measurement of cerebral hemodynamics and electroencephalography during transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is currently being used for research and treatment of some neurological and neuropsychiatric disorders, as well as for improvement of cognitive functions. In order to better understand cerebral response to the stimulation and to redefine protocols and dosage, its effects must be monitored. To this end, we have used functional diffuse correlation spectroscopy (fDCS) and time-resolved functional near-infrared spectroscopy (TR-fNIRS) together with electroencephalography (EEG) during and after stimulation of the frontal cortex. Twenty subjects participated in two sessions of stimulation with two different polarity montages and twelve also underwent a sham session. Cerebral blood flow and oxyhemoglobin concentration increased during and after active stimulation in the region under the stimulation electrode while deoxyhemoglobin concentration decreased. The EEG spectrum displayed statistically significant power changes across different stimulation sessions in delta (2 to 4 Hz), theta (4 to 8 Hz), and beta (12 to 18 Hz) bands. Results suggest that fDCS and TR-fNIRS can be employed as neuromonitors of the effects of transcranial electrical stimulation and can be used together with EEG.Peer ReviewedPostprint (published version

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Hybrid diffuse optical neuromonitoring of cerebral haemodynamics: from the smallest premature born infants to adults

Aplicat embargament des de la data de defensa fins al dia 1 de juny de 2021Hybrid diffuse optical devices allows for the non-invasive and continuous monitoring of the cerebral haemodynamics and metabolism. Such devices can be portable and are relatively inexpensive, therefore available at the bed- or cot side. These advantages make the technology appealing and useful for a variety of applications. For my Ph.D. thesis, I have worked on the development of new devices that integrate diffuse correlation (DCS) and time resolved near-infrared spectroscopy (TRS) and on broadening their field of applications. Preterm newborn infants are one of the target populations for such a neuromonitor. Premature newborns are at a risk of impaired neurodevelopment due to brain lesions that can be developed during first hours and days of life. In spite of the fact that these lesions are often due to episodes of abnormalities of the cerebral haemodynamics, related to oxygen supply to the brain and its consumption, these parameters are not currently monitored due to the lack of an appropriate technology. In order to meet this need, the BabyLux project aimed at developing a hybrid diffuse optical device that could be used to assess the cerebral well-being of the premature newborn infants. In the framework of this project, I have developed and built the Baby-Lux device. Specifically, I have integrated DCS, to measure microvascular blood ow, and TRS, to measure microvascular blood oxygenation, into a user-friendly device, a prototype for a future medical grade device. In this thesis I report results of tests in laboratory settings in order to assess the device performance in best-case scenario. Furthermore, I explore the device's limits in precision and accuracy, through simulated DCS and TRS data with realistic noise added, and I describe the influence of a variety of experimental and analysis parameters. In addition, I demonstrate a high correlation between cerebral blood ow (CBF) measurement performed by the BabyLux device and by the gold standard positron emission tomography with 15O-labeled water on a neonatal piglet model. This proves the robustness of the BabyLux solution for blood ow measurement and provides a calibration formula to convert the DCS-measured blood ow index into traditional ow units. Finally, the device was tested in clinical settings, on healthy term newborns. It allowed for following cerebral haemodynamics and metabolism during the transition after birth. Reproducibility over probe replacement appeared improved with respect to commercial oximeters for tissue blood oxygen saturation and comparable to other technologies for the blood ow. For an additional study on adult healthy volunteers, I have constructed a hybrid device integrating a commercial DCS and a prototype for a TRS device. This could serve as a neuro-monitor for following the cerebral response to transcranial direct current stimulation. This is a non-invasive form of stimulating the brain that has proven to be effective for cognitive augmentation and for treating pathological conditions.In conclusion, the work presented in this thesis paves the way to a new generation of neonatal neuro-monitors that can be developed for extensive, multi-center clinical testing and ultimately allow a robust and accurate assessment of the cerebral well-being of the newborns. As far as the adult brain is concerned, I have introduced a new method for monitoring the cerebral response during transcranial direct current stimulation that can be exploited for protocol and dosage definition and, eventually, for the on-line monitoring of the cerebral response to the stimulation, tailoring the intervention to each subject's condition.Las tecnologías de óptica difusa permiten estimar de manera no invasiva y continua la hemodinámica y el metabolismo cerebral a través de instrumentos manejables, de coste relativamente bajo y disponibles al lado de la cama o la cuna del paciente. En mi tesis doctoral he desarrollado un instrumento que combina dos técnicas de óptica difusa: diffuse correlation spectroscopy (DCS) y time resolved near-infrared spectroscopy" (TRS). Además, he contribuido a explorar nuevas aplicaciones para estas tecnologías. Los prematuros recién nacidos son unas de las poblaciones objetivos para este tipo de aparato de monitorización cerebral. El desarrollo cerebral de los prematuros es más susceptible de lesiones cerebrales desarrolladas en las primeras horas o días de vida. Aunque estas lesiones cerebrovasculares son generalmente causadas por anomalías en la hemodinámica cerebral, es decir en el flujo sanguíneo hacia el cerebro o en el nivel de oxigenación del tejido cerebral, estos parámetros no son monitorizados de forma continua porque no existe una tecnología que permita hacerlo. El proyecto Baby Lux, en el que participé activamente, tenía el objetivo de desarrollar un instrumento que utilizara óptica difusa para monitorizar el cerebro de los bebés prematuros. Con el consorcio del proyecto Baby Lux, he desarrollado y construido un aparato que combina DCS, para medir el flujo sanguíneo micro-vascular, y TRS, que mide la oxigenación del flujo microvascular, con el objetivo de que fuera preciso, exacto y sólido como para poder utilizarse en aplicaciones clínicas. En esta tesis se exploran sus límites de precisión y exactitud, simulando datos DCS y TRS, y cómo estos se ven influenciados por varios parámetros experimentales y de análisis. Además, se demuestra una fuerte correlación en lechones entre el flujo sanguíneo medido por Baby Lux y lo medido por tomografía por emisión de positrones (PET) con 15O como radiofármaco, técnica de referencia para medir el flujo sanguíneo cerebral. Esto demuestra la habilidad de la medida de flujo de Baby Lux y, además, permite calibrar el flujo sanguíneo medido por la DCS y convertirlo en la unidad tradicional de medida de flujo. Finalmente, el dispositivo fue ensayado en hospitales. La hemodinámica cerebral fue monitorizada en los minutos posteriores al nacimiento de bebés sanos. La reproducibilidad de las medidas de Baby Lux demostró una calidad superior respecto a los oxímetros cerebrales actuales y comparables a otras tecnologías para medir el flujo cerebral. Estudios adicionales han investigado la hemodinámica cerebral de voluntarios adultos y sanos con otro aparato que he construido combinando una DCS comercial y un prototipo para una TRS. He demostrado que este aparato puede ser útil para investigar la respuesta cerebral a la estimulación eléctrica transcraneal, una forma de estimulación no invasiva que ha dado buenos resultados para tratar condiciones patológicas o para mejorar capacidades cognitivas. En resumen, el trabajo presentado en esta tesis abre el camino hacia una nueva generación de instrumentos capaces de monitorizar el cerebro de los bebés prematuros, que puedan ser utilizados en ensayos clínicos en varios hospitales y de forma extensiva. Además, he introducido una nueva técnica para monitorizar la respuesta cerebral a la estimulación transcraneal que pueda ayudar a la hora de definir protocolos y dosis de la estimulación y que permite adaptar el protocolo a cada sujeto.Postprint (published version

Long-lasting, liquid phantom for diffuse optical and correlation spectroscopies

A long-lasting (>2 months), stable liquid phantom suitable for longitudinal testing and calibration of diffuse optical and correlation spectroscopies is presented