Photoacoustic imaging of squirrel monkey cortical and subcortical brain regions during peripheral electrical stimulation

The investigation of neuronal activity in non-human primate models is of critical importance due to their genetic similarity to human brains. In this study, we tested the feasibility of using photoacoustic imaging for the detection of cortical and subcortical responses due to peripheral electrical stimulation in a squirrel monkey model. Photoacoustic computed tomography and photoacoustic microscopy were applied on squirrel monkeys for real-time deep subcortical imaging and optical-resolution cortical imaging, respectively. The electrically evoked hemodynamic changes in primary somatosensory cortex, premotor cortices, primary motor cortex, and underlying subcortical areas were measured. Hemodynamic responses were observed in both cortical and subcortical brain areas at the cortices during external stimulation, demonstrating the feasibility of photoacoustic technique for functional imaging of non-human primate brain

DYNAMIC SELF-ORGANISED NEURAL NETWORK INSPIRED BY THE IMMUNE ALGORITHM FOR FINANCIAL TIME SERIES PREDICTION AND MEDICAL DATA CLASSIFICATION

Artificial neural networks have been proposed as useful tools in time series analysis in a variety of applications. They are capable of providing good solutions for a variety of problems, including classification and prediction. However, for time series analysis, it must be taken into account that the variables of data are related to the time dimension and are highly correlated. The main aim of this research work is to investigate and develop efficient dynamic neural networks in order to deal with data analysis issues. This research work proposes a novel dynamic self-organised multilayer neural network based on the immune algorithm for financial time series prediction and biomedical signal classification, combining the properties of both recurrent and self-organised neural networks. The first case study that has been addressed in this thesis is prediction of financial time series. The financial time series signal is in the form of historical prices of different companies. The future prediction of price in financial time series enables businesses to make profits by predicting or simply guessing these prices based on some historical data. However, the financial time series signal exhibits a highly random behaviour, which is non-stationary and nonlinear in nature. Therefore, the prediction of this type of time series is very challenging. In this thesis, a number of experiments have been simulated to evaluate the ability of the designed recurrent neural network to forecast the future value of financial time series. The resulting forecast made by the proposed network shows substantial profits on financial historical signals when compared to the self-organised hidden layer inspired by immune algorithm and multilayer perceptron neural networks. These results suggest that the proposed dynamic neural networks has a better ability to capture the chaotic movement in financial signals. The second case that has been addressed in this thesis is for predicting preterm birth and diagnosing preterm labour. One of the most challenging tasks currently facing the healthcare community is the identification of preterm labour, which has important significances for both healthcare and the economy. Premature birth occurs when the baby is born before completion of the 37-week gestation period. Incomplete understanding of the physiology of the uterus and parturition means that premature labour prediction is a difficult task. The early prediction of preterm births could help to improve prevention, through appropriate medical and lifestyle interventions. One promising method is the use of Electrohysterography. This method records the uterine electrical activity during pregnancy. In this thesis, the proposed dynamic neural network has been used for classifying between term and preterm labour using uterine signals. The results indicated that the proposed network generated improved classification accuracy in comparison to the benchmarked neural network architectures

Point-of-Care Detection Devices for Healthcare

With recent technological advances in multiple research fields such as materials science, micro-/nano-technology, cellular and molecular biology, bioengineering and the environment, much attention is shifting toward the development of new detection tools that not only address needs for high sensitivity and specificity but fulfil economic, environmental, and rapid point-of-care needs for groups and individuals with constrained resources and, possibly, limited training. Miniaturized fluidics-based platforms that precisely manipulate tiny body fluid volumes can be used for medical, healthcare or even environmental (e.g., heavy metal detection) diagnosis in a rapid and accurate manner. These new detection technologies are potentially applicable to different healthcare or environmental issues, since they are disposable, inexpensive, portable, and easy to use for the detection of human diseases or environmental issues—especially when they are manufactured based on low-cost materials, such as paper. The topics in this book (original and review articles) would cover point-of-care detection devices, microfluidic or paper-based detection devices, new materials for making detection devices, and others

European position paper on rhinosinusitis and nasal polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.Peer reviewe

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Investigating accuracy and precision of ionoacoustics for range determination of ion beams in water

Bei der externen Strahlentherapie wird Patienten Dosis mithilfe von hochenergetischen Photonen oder geladenen Teilchen, hauptsächlich Protonen zugeführt. Aufgrund der geringeren Kosten im Kauf und Unterhalt klinischer Photonenanlagen werden diese derzeit bevorzugt, obwohl die Dosisverteilung im Patienten weniger präzise ist als mit Protonenstrahlen. Der Grund dafür ist das exponentielle Abschwächungsverhalten energetischer Photonen in Materie, womit ein signifikanter Anteil an zusätzlicher Dosis in umliegendem, gesundem Gewebe in Kauf genommen werden muss. Protonen weisen ein Tiefendosisprofil in der Form der sog. Braggkurve mit einer scharf begrenzten, endlichen Reichweite auf, sodass in Einstrahlrichtung Risikoorgane vor unnötiger Dosis geschützt werden können. Aufgrund von Reichweitenungenauigkeiten, einem der größten, technischen Probleme moderner Strahlentherapie, werden Sicherheitssäume eingeplant und der Vorteil in der Dosisverteilung, der sich aus dem unterschiedlichen physikalischen Absorptionsverhalten von Photonen und Protonen ergibt, wird aufgegeben. Diese Ungenauigkeiten sind bedingt durch diverse praktische Begrenzungen während der Bestrahlung, wie zum Beispiel dem Atemzyklus des Patienten oder andere intrafraktionale Organbewegungen, oder durch Veränderungen zwischen den Behandlungstagen, wie Gewichtsverlust oder die innere Verschiebung der Organe von Tag zu Tag. Einen möglichen Ansatz, diese Reichweitenungenauigkeit zu verringern, bietet hierbei die in-vivo Dosimetrie, eine Methode, die idealerweise in Echtzeit die zugeführte Dosis, oder zumindest die Reichweite, im Patienten messen, verifizieren und darstellen kann. Dafür ist in den letzten Jahrzehnten vor allen an zwei Abbildungsmethoden basierend auf der Detektion der durch Kernreaktionen induzierten Sekundärstrahlung geforscht worden: Messungen der Positronen-Emissionen ausgelöst durch die Bestrahlung und Prompt-ɣ-Monitoring. Auch wenn bereits erste Prototypen in klinischen Studien getestet werden, handelt es sich hierbei um anspruchsvolle nuklearphysikalische Experimente, für die bisher mitunter komplexe Rechnungen und Rekonstruktionen nötig waren, was im Gegensatz zu der Forderung nach einer Echtzeitmethode stand. Auch wenn z.B. mit der Entwicklung der Einzelschlitz-Prompt-ɣ Kamera ein großer Fortschritt in der Überwindung dieser Probleme erreicht wurde, möchte diese Arbeit eine alternative Methode der Reichweitenbestimmung erneut aufgreifen: Ionoakustik. Es soll in dieser Arbeit gezeigt werden, dass es sich dabei um eine kostengünstige Möglichkeit handelt, um quasi in Echtzeit Informationen über die tatsächliche Bragg Peak Position zu erhalten. Bei der Bestrahlung mit gepulsten Ionenstrahlen kann eine Ultraschallwelle gemessen werden, welche räumliche und zeitliche Information über den Ionenpuls und die auslösende adiabatische Erwärmung in sich trägt. Ionoakustik ist die Messung und Auswertung dieser Ultraschallwelle, um die Energie und Reichweite der geladenen Teilchen zu bestimmen. In dieser Arbeit wird die grundlegende Erzeugung des Druckes erklärt, welche Einflüsse während der Messung auf das Signal auftreten, und wie die gemessenen Signale auszuwerten sind. Im Rahmen dieser Arbeit wurden verschiedene Experimente an unterschiedlichen Beschleunigern durchgeführt. Hierbei wurden zahlreiche Messungen mit ausreichendem Signal-zu-Rausch-Verhältnis gemacht und die dabei gemessenen Reichweiten werden präsentiert. Es konnten bei Protonen mit einer kinetischen Energie von 20 MeV Reichweiten im Wasser mit einer Genauigkeit und Präzision von weniger als 50µm gemessen werden. An medizinischen Beschleunigern mit >200 MeV Protonen wurden Reichweiten im Wasser mit einer Genauigkeit und Präzision von weniger als 1 mm gemessen, bei anderen schweren Ionen war die Genauigkeit und Präzision weniger als 100 µm. Dabei steht die mögliche Übertragbarkeit in eine medizinische Anwendung besonders im Fokus der Diskussionen, da diese guten Ergebnisse die Verringerung der Sicherheitssäume in der Behandlungsplanung zur Folge haben könnten und damit eine Verbesserung der Bestrahlung mit geladenen Teilchen im Allgemeinen. Die hier vorgestellten experimentellen Ergebnisse beinhalten Messungen von verschieden kinetischen Energien, unterschiedlichen Ionen und Intensitäten. In allen Fällen zeigten vergleichende Simulationsrechnungen gute Übereinstimmungen. Besonders in Messungen, in denen die experimentellen Parameter sehr detailliert bestimmt werden konnten, können diese Messung als Bestätigung von Simulationsparametern interpretiert werden, obwohl diese Parameter normalerweise zur Anpassung an Messwerte Variationen unterzogen werden. Das hier verwendete Ionisationspotential für Wasser mit einem Wert von 78 eV, die derzeit gültige Empfehlung der Internationalen Kommission für Strahlungseinheiten und Messung ICRU, zeigte in den hier durchgeführten Studien die beste Übereinstimmung mit den Messergebnissen. Die mögliche Einsetzbarkeit ist derzeit auf Regionen beschränkt, die mit klinischem Ultraschall abgebildet werden können. Die technische Machbarkeit und nötige nächste Schritte werden diskutiert und mit einem möglichen Behandlungsszenario abgeschlossen, welches akustische Messungen einbezieht. Hierbei ist die derzeitige größte Herausforderung die immer noch hohe Dosis, die benötigt wird, um hinreichende ionoakustische Signale zu erzeugen.In radiation therapy using external beams, delivery of dose is currently done with energetic photons or heavy charged particles, mainly protons. The treatment with photons is favoured as installation and maintenance costs are lower than with proton therapy, although the delivered dose distribution is less confined in space. This is due to the exponentially decaying depth dose distribution of photons in matter, adding a significant dose to tissue surrounding the tumour site. Protons, on the contrary, have a finite penetration depth in matter and a distinct maximum of deposited energy, the Bragg peak, both mainly depending on the initial kinetic energy of the incident heavy charged particle. This offers spatially confined dose distributions compared to the irradiation with photons, if the range of heavy charged particle in tissue is known precisely. However, due to several practical limitations, relatively large safety margins are added in the treatment planning in order to compensate for range uncertainties, e.g. limited knowledge on the tissue stopping power as well as changes in the patient anatomy during a single treatment, like breathing and other intra-fractional organ motions, and between several treatment days, like weight loss and large scale organ displacements. These range uncertainties are one of the biggest challenges in modern radiation therapy with heavy charged particles, thus hampering the potential superiority of this irradiation modality in terms of dose conformity A practical approach which would allow a reduction of these safety margins would be in-vivo-dosimetry, an online method verifying and displaying the currently delivered dose, or at least the beam range, to the patient. To this end, methods based on secondary radiation induced by nuclear interactions have been studied over the last decades, and at least two promising approaches have reached the status of clinical trials. However, Positron-Emission-Tomography and prompt-ɣ monitoring require relatively bulky and expensive instrumentation as well as complex simulations and reconstructions. Although considerable progress has been made with the development of a single-slit prompt-ɣ device, in the past the previously mentioned problems were hindering these approaches to become truly online methods. In this thesis, Ionoacoustics is revisited as a range determination mechanism offering a cost-effective technology providing quasi real-time informations on the actual Bragg peak position. Following irradiation with a pulsed ion beam, a pressure wave is measured, which contains spatial and temporal information on the initiating adiabatic heating. The evaluation of the pressure signal in order to extract energy, specifically range information, is called Ionoacoustics. In this framework, the basis of the pressure generation and detection is thoroughly studied together with different evaluation techniques. Several experiments at different accelerators have been conducted, which provided measurements with a good signal to noise ratio, and their results are discussed. It can be shown that ranges of 20 MeV protons in water can be determined with a precision and accuracy better than 50 µm, the range of high energetic protons under clinical condition better than 1 mm, and other heavy ions better than 100 µm. It will be discussed, whether the translation of these precise results to clinical applications is feasible, as this would lower the currently used safety margins used in treatment planning. The presented experiments cover a wide range of particle energies, ion types, and intensities. Simulation studies showed very good agreement to the collected experimental results. Especially for the studies at low-energies, where experimental parameters are defined precisely, simulation parameters can be confirmed. The ionization potential of water of 78 eV following the latest recommendation of the International Commission on Radiation Units and Measurements ICRU yielded results in best agreement to experimental data. The technical feasibility and next required steps will be discussed concluding with a possible scenario for treatment verification with acoustic measurements for a favourable anatomical indication of viable sonic accessibility. The currently biggest challenge in this step towards a clinical application is the still high dose that is required to generate ionoacoustic signals

Motion quantification and automated correction in clinical RSOM.

Raster-scan optoacoustic mesoscopy (RSOM) offers high-resolution non-invasive insights into skin pathophysiology, which holds promise for disease diagnosis and monitoring in dermatology and other fields. However, RSOM is quite vulnerable to verticalmotion of the skin, which can depend on the part of the body being imaged. Motion correction algorithms have already been proposed, but they are not fully automated, they depend on anatomical segmentation pre-processing steps that might not be performed successfully, and they are not site-specific. Here, we determined for the first time the magnitude of themicrometric vertical skin displacements at different sites on the body that affect RSOM. The quantification of motion allowed us to develop a site-specific correction algorithm. The algorithm is fully automated and does not need prior anatomical information. We found that the magnitude of the vertical motion depends strongly on the site of imaging and is caused by breathing, heart beating, and arterial pulsation. The developed algorithm resulted in more than 2-fold improvement in the signal-to-noise ratio of the reconstructed images at every site tested. Proposing an effective automatedmotion correction algorithm paves the way for realizing the full clinical potential of RSOM