MR imaging–derived oxygen-hemoglobin dissociation curves and fetal-placental oxygen-hemoglobin affinities

PURPOSE: To generate magnetic resonance (MR) imaging–derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level–dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. MATERIALS AND METHODS: All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%–10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%–100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging–based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. RESULTS: The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P < .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003). Reproduction of the MR imaging–based oxygen-hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. CONCLUSION: MR imaging–based oxygen-hemoglobin dissociation curves and oxygen-hemoglobin affinity information were derived for pregnant mice by using 9.4-T MR imaging, which suggests a potential to overcome the need for direct sampling of fetal or maternal blood. Online supplemental material is available for this article

A comparative study of the dosimetric features of α-Al2O3: C, Mg and α-Al2O3: C

A comparative study of the dosimetric features of α-Al2O3:C,Mg and α-Al2O3:C relevant to thermoluminescence dosimetry is reported. A glow curve of α-Al2O3:C,Mg measured at 1°C/s after beta irradiation to 1 Gy shows two subsidiary peaks at 42°C (labelled as I) and 72°C (II) and the main peak at 161°C (III) whereas a glow curve of α-Al2O3:C measured under the same conditions shows the main peak at 178°C (II′) and a lower intensity peak at 48°C (I′). Apart from these ones, there are several other peaks at temperatures beyond that of the main peak in both α-Al2O3:C,Mg and α-Al2O3:C. However, the latter are not included in this study. We report a comparative quantitative analysis of dose response and fading of peaks I, II and III of α-Al2O3:C,Mg and peaks I′ and II′ of α-Al2O3:C. Analysis shows that the dose response of peaks I and III is sublinear within 1–10 Gy whereas that of peak II is superlinear within 1–4 Gy followed by a sublinear region within 4–10 Gy. In comparison, the dose response of peak I′ is superlinear within 1–4 Gy followed by a sublinear region within 4–10 Gy whereas that of peak II′ is sublinear within 1–4 Gy followed by a superlinear region within 4–10 Gy. As regards to fading corresponding to 1 Gy, peak I is very unstable and fades within 300 s, peak II is more stable and takes up to 43200 s to fade. In comparison, peak III fades down to 30% of its initial intensity within 2400 s. Interestingly, between 2400 and 800 s, the intensity fades by 17% only. Regarding fading in α-Al2O3:C, peak I′ fades within 600 s whereas peak II′ shows an inverse fading behaviour up to 64800 s. The rate of fading for peaks I, II and III in α-Al2O3:C,Mg was found to decrease with increase in dose. However, no such behaviour was observed in α-Al2O3:C. The fading in both samples is discussed on the basis of a charge hopping mechanism

Multiscale body maps in the human brain

A large number of brain regions are dedicated to processing information from the body in order to enable interactions with the environment. During my thesis, I studied the functional organization of brain networks involved in processing bodily information. From the processing of unimodal low-level features to the unique experience of being a unified entity residing in a physical body, the brain processes and integrates bodily information at many different stages. Using ultra high-field functional Magnetic Resonance Imaging (fMRI), I conducted four studies to map and characterize multiscale body representations in the human brain. The goals of my thesis were first to extend the actual knowledge about primary sensorimotor representations, and second to develop novel approaches to investigate more complex and integrated forms of body representations. In studies I and II, I first investigated how natural touch was represented in the three first cortical areas processing tactile information. I applied a mapping procedure to identify in each of these three areas the somatosensory representations of 24 different body parts on hands, feet and legs at the level of single subjects. Using fMRI and resting-state data, I combined classical statistical analyses with modern methods of network analysis to describe the functional properties of the formed network. In study III, I applied these methods to investigate primary somatosensory and motor representations in a rare population of patients. Following limb loss, the targeted muscle and sensory reinnervation (TMSR) procedure enables the intuitive control of a myoelectric prosthesis and creates an artificial map of referred touch on the reinnervated skin. I mapped the primary somatosensory and motor representations of phantom sensations and phantom movements in TMSR patients. I investigated whether sensorimotor training enabled via TMSR was associated with preserved somatosensory and motor representations compared to healthy controls and amputee patients without TMSR. Finally in study IV, I studied brain regions involved in the subjective body experience. Following specific manipulations of sensorimotor information, it is possible to let participants experience a fake or virtual hand as their own and to give them the sensation of being in control of this hand. Using MR-compatible robotics and virtual reality, I investigated the brain regions associated with the alteration of the sense of hand ownership and the sense of hand agency. The present work provides important findings and promising tools regarding the understanding of brain networks processing bodily information. In particular, understanding the functional interactions between primary unimodal cortices and networks contributing to subjective body experience is a necessity to promote modern approaches in the fields of neuroprosthetic and human-machine interactions

Quality of service and dependability of cellular vehicular communication networks

Improving the dependability of mobile network applications is a complicated task for many reasons: Especially in Germany, the development of cellular infrastructure has not always been fast enough to keep up with the growing demand, resulting in many blind spots that cause communication outages. However, even when the infrastructure is available, the mobility of the users still poses a major challenge when it comes to the dependability of applications: As the user moves, the capacity of the channel can experience major changes. This can mean that applications like adjustable bitrate video streaming cannot infer future performance by analyzing past download rates, as it will only have old information about the data rate at a different location. In this work, we explore the use of 4G LTE for dependable communication in mobile vehicular scenarios. For this, we first look at the performance of LTE, especially in mobile environments, and how it has developed over time. We compare measurements performed several years apart and look at performance differences in urban and rural areas. We find that even though the continued development of the 4G standard has enabled better performance in theory, this has not always been reflected in real-life performance due to the slow development of infrastructure, especially along highways. We also explore the possibility of performance prediction in LTE networks without the need to perform active measurements. For this, we look at the relationship between the measured signal quality and the achievable data rates and latencies. We find that while there is a strong correlation between some of the signal quality indicators and the achievable data rates, the relationship between them is stochastic, i.e., a higher signal quality makes better performance more probable but does not guarantee it. We then use our empirical measurement results as a basis for a model that uses signal quality measurements to predict a throughput distribution. The resulting estimate of the obtainable throughput can then be used in adjustable bitrate applications like video streaming to improve their dependability. Mobile networks also task TCP congestion control algorithms with a new challenge: Usually, senders use TCP congestion control to avoid causing congestion in the network by sending too many packets and so that the network bandwidth is divided fairly. This can be a challenging task since it is not known how many senders are in the network, and the network load can change at any time. In mobile vehicular networks, TCP congestion control is confronted with the additional problem of a constantly changing capacity: As users change their location, the quality of the channel also changes, and the capacity of the channel can experience drastic reductions even when the difference of location is very small. Additionally, in our measurements, we have observed that packet losses only rarely occur (and instead, packets are delayed and retransmitted), meaning that loss-based algorithms like Reno or CUBIC can be at a significant disadvantage. In this thesis, we compare several popular congestion control algorithms in both stationary and mobile scenarios. We find that many loss-based algorithms tend to cause bufferbloat and thus overly increase delays. At the same time, many delay-based algorithms tend to underestimate the network capacity and thus achieve data rates that are too low. The algorithm that performed the best in our measurements was TCP BBR, as it was able to utilize the full capacity of the channel without causing bufferbloat and also react to changes in capacity by adjusting its window. However, since TCP BBR can be unfair towards other algorithms in wired networks, its use could be problematic. Finally, we also propose how our model for data rate prediction can be used to improve the dependability of mobile video streaming. For this, we develop an algorithm for adaptive bitrate streaming that provides a guarantee that the video freeze probability does not exceed a certain pre-selected upper threshold. For the algorithm to work, it needs to know the distribution of obtainable throughput. We use a simulation to verify the function of this algorithm using a distribution obtained through the previously proposed data rate prediction algorithm. In our simulation, the algorithm limited the video freeze probability as intended. However, it did so at the cost of frequent switches of video bitrate, which can diminish the quality of user experience. In future work, we want to explore the possibility of different algorithms that offer a trade-off between the video freeze probability and the frequency of bitrate switches.Die Verbesserung der Zuverlässigkeit von mobilen Netzwerk-basierten Anwendungen ist aus vielen Gründen eine komplizierte Aufgabe: Vor allem in Deutschland war die Entwicklung der Mobilfunkinfrastruktur nicht immer schnell genug, um mit der wachsenden Nachfrage Schritt zu halten. Es gibt immer noch viele Funklöchern, die für Kommunikationsausfälle verantwortlich sind. Aber auch an Orten, an denen Infrastruktur ausreichend vorhanden ist, stellt die Mobilität der Nutzer eine große Herausforderung für die Zuverlässigkeit der Anwendungen dar: Wenn sich der Nutzer bewegt, kann sich die Kapazität des Kanals stark verändern. Dies kann dazu führen, dass Anwendungen wie Videostreaming mit einstellbarer Bitrate die in der Vergangenheit erreichten Downloadraten nicht zur Vorhersage der zukünftigen Leistung nutzen können, da diese nur alte Informationen über die Datenraten an einem anderen Standort enthalten. In dieser Arbeit untersuchen wir die Nutzung von 4G LTE für zuverlässige Kommunikation in mobilen Fahrzeugszenarien. Zu diesem Zweck untersuchen wir zunächst die Leistung von LTE, insbesondere in mobilen Umgebungen, und wie sie sich im Laufe der Zeit entwickelt hat. Wir vergleichen Messungen, die in einem zeitlichen Abstand von mehreren Jahren durchgeführt wurden, und untersuchen Leistungsunterschiede in städtischen und ländlichen Gebieten. Wir stellen fest, dass die kontinuierliche Weiterentwicklung des 4G-Standards zwar theoretisch eine bessere Leistung ermöglicht hat, dass sich dies aber aufgrund des langsamen Ausbaus der Infrastruktur, insbesondere entlang von Autobahnen, nicht immer in der Praxis bemerkbar gemacht hat. Wir untersuchen auch die Möglichkeit der Leistungsvorhersage in LTE-Netzen, ohne aktive Messungen durchführen zu müssen. Zu diesem Zweck untersuchen wir die Beziehung zwischen der gemessenen Signalqualität und den erreichbaren Datenraten und Latenzzeiten. Wir stellen fest, dass es zwar eine starke Korrelation zwischen einigen der Signalqualitätsindikatoren und den erreichbaren Datenraten gibt, die Beziehung zwischen ihnen aber stochastisch ist, d. h. eine höhere Signalqualität macht eine bessere Leistung zwar wahrscheinlicher, garantiert sie aber nicht. Wir verwenden dann unsere empirischen Messergebnisse als Grundlage für ein Modell, das die Signalqualitätsmessungen zur Vorhersage einer Durchsatzverteilung nutzt. Die sich daraus ergebende Schätzung des erzielbaren Durchsatzes kann dann in Anwendungen mit einstellbarer Bitrate wie Videostreaming verwendet werden, um deren Zuverlässigkeit zu verbessern. Mobile Netze stellen auch TCP Congestion Control Algorithmen vor eine neue Herausforderung: Normalerweise verwenden Sender TCP Congestion Control, um eine Überlastung des Netzes durch das Senden von zu vielen Paketen zu vermeiden, und um die Bandbreite des Netzes gerecht aufzuteilen. Dies kann eine schwierige Aufgabe sein, da es nicht bekannt ist, wie viele Sender sich im Netz befinden, und sich die Netzlast jederzeit ändern kann. In mobilen Fahrzeugnetzen ist TCP Congestion Control mit dem zusätzlichen Problem einer sich ständig ändernden Kapazität konfrontiert: Wenn die Benutzer ihren Standort wechseln, ändert sich auch die Qualität des Kanals, und die Kanalkapazität des Kanals kann drastisch sinken, selbst wenn der Unterschied zwischen den Standorten sehr gering ist. Darüber hinaus haben wir bei unseren Messungen festgestellt, dass Paketverluste nur selten auftreten (stattdessen werden Pakete verzögert und erneut übertragen), was bedeutet, dass verlustbasierte Algorithmen wie Reno oder CUBIC einen großen Nachteil haben können. In dieser Arbeit vergleichen wir mehrere gängige Congestion Control Algorithmen sowohl in stationären als auch in mobilen Szenarien. Wir stellen fest, dass viele verlustbasierte Algorithmen dazu neigen, einen Pufferüberlauf zu verursachen und somit die Latenzen übermäßig erhöhen, während viele latenzbasierte Algorithmen dazu neigen, die Kanalkapazität zu unterschätzen und somit zu niedrige Datenraten erzielen. Der Algorithmus, der bei unseren Messungen am besten abgeschnitten hat, war TCP BBR, da er in der Lage war, die volle Kapazität des Kanals auszunutzen, ohne den Pufferfüllstand übermäßig zu erhöhen. Ebenso hat TCP BBR schnell auf Kapazitätsänderungen reagiert, indem er seine Fenstergröße angepasst hat. Da TCP BBR jedoch in kabelgebundenen Netzen gegenüber anderen Algorithmen unfair sein kann, könnte seine Verwendung problematisch sein. Schließlich schlagen wir auch vor, wie unser Modell zur Vorhersage von Datenraten verwendet werden kann, um die Zuverlässigkeit des mobilen Videostreaming zu verbessern. Dazu entwickeln wir einen Algorithmus für Streaming mit adaptiver Bitrate, der garantiert, dass die Wahrscheinlichkeit des Anhaltens eines Videos eine bestimmte, vorher festgelegte Obergrenze nicht überschreitet. Damit der Algorithmus funktionieren kann, muss er die Verteilung des erreichbaren Durchsatzes kennen. Wir verwenden eine Simulation, um die Funktion dieses Algorithmus zu überprüfen. Hierzu verwenden wir eine Verteilung, die wir durch den zuvor vorgeschlagenen Algorithmus zur Vorhersage von Datenraten erhalten haben. In unserer Simulation begrenzte der Algorithmus die Wahrscheinlichkeit des Anhaltens von Videos wie beabsichtigt, allerdings um den Preis eines häufigen Wechsels der Videobitrate, was die Qualität der Benutzererfahrung beeinträchtigen kann. In zukünftigen Arbeiten wollen wir die Möglichkeit verschiedener Algorithmen untersuchen, die einen Kompromiss zwischen der Wahrscheinlichkeit des Anhaltens des Videos und der Häufigkeit der Bitratenwechsel bieten

Electrocardiogram derived respiration during sleep

The aim of this study was quantify the ECG Derived Respiration (EDR) in order to extend the capabilities of ECG-based sleep analysis. We examined our results in normal subjects and in patients with Obstructive Sleep Apnea Syndrome (OSAS) or Central Sleep Apnea. Lead 2 ECG and three measures of respiration (thorax and abdominal effort, and oronasal flow signal) were recorded during sleep studies of 12 normal and 12 OSAS patients. Three parameters, the R-wave amplitude (RWA), R-wave duration (RWD), and QRS area, were extracted from the ECG signal, resulting in time series that displayed a behavior similar to that of the respiration signals. EDR frequency was correlated with directly measured respiratory frequency, and averaged over all subjects. The peak-to-peak value of the EDR signals during the apnea event was compared to the average peak-to-peak of the sleep stage, containing the apnea. 1

Changes in Heart Rate Variability Recorded in Natural Situation with T-Shirt Integrated Sensors and Level of Observed Behavioral Excitation: A Pilot Study of Patients with Intellectual Disabilities and Psychiatric Disorders.

The present study investigates the possibilities of using heart rate variability (HRV) parameters as physiological markers that precede increase in observed behavioral excitation of intellectually disabled individuals. The ability to recognize or predict such patterns, especially in patients showing unpredictable reactions and language deficiencies, might be a major step forward in clinical research. Thirteen volunteers with intellectual disabilities, who had suffered of at least one event of overt aggression in the preceding 3 months, participated to the study. The protocol consists in the acquisition of continuous electrocardiogram (ECG) throughout approximately two times of 8 h in natural situation, using a T-shirt integrated with sensors. Simultaneously, an observer evaluates the patient's level of overt excitation from calm (level 1) to extremely tense (level 5) and send online via Bluetooth these triggers into the ECG signals. The HRV indexes were then estimated offline on the basis of the inter-beat intervals recorded by the ECG, independently for the 30 min preceding each behavioral tension marking point, averaged, and compared through non-parametric Wilcoxon matched-pairs test. Of these, the RMSSD and LF/HF calculations were used to observe the fluctuations of inhibitory activity and cardiovagal balance through different tension states. Seven individuals have sufficient reliable data for analysis. They have reached at least a level 3 of behavioral excitation (moderately tense) or more (very to extremely tense, level 4 and 5) and have been retained for further analysis. In sum, a total of 197 periods of tension were kept, made up of 46 periods of slight excitation (level 2), 18 of moderate excitation (level 3), 10 of high excitation (level 4), and 5 of extreme agitation (level 5). Variations in the HRV as a function of degree of excitation are observed for RMSSD index only (inhibitory parasympathetic activity). The changes from calm to increasing levels of excitation are characterized by a significant downfall in RMSSD index when patients were evaluated to be in a very high level of tension (level 4). The presence of precursors to agitation, reflected in the falling-off of parasympathetic activity, offers potentially interesting prospects for therapeutic development

Ion range measurements using fluorescent nuclear track detectors

Fluorescent nuclear track detectors (FNTDs) show excellent detection properties for heavy charged particles and have, therefore, been investigated in this study in terms of their potential for in-vivo range measurements. We irradiated FNTDs with protons as well as with C, Mg, S, Fe and Xe ion beams (3 – 9 MeV/u) over a broad range of fluences (4.5e5 – 1.0e11 per cm²) with the detectors’ optical c-axis positioned perpendicular to the beam direction. All measured ion ranges (for single track as well as track bulk intensity irradiations) deviate less than 3% from tabulated SRIM data, independent of particle type, energy, fluence and linear energy transfer. Proton irradiation of detectors placed inside a polymethyl methacrylate (PMMA) phantom at the Heidelberg Ion-Beam Therapy Center showed promising results for future in-vivo FNTD applications