Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy—Use of Greenhouses and Artificial Light Sources

Daylight-mediated photodynamic therapy (daylight PDT) is a simple and pain free treatment of actinic keratoses. Weather conditions may not always allow daylight PDT outdoors. We compared the spectrum of five different lamp candidates for indoor “daylight PDT” and investigated their ability to photobleach protoporphyrin IX (PpIX). Furthermore, we measured the amount of PpIX activating daylight available in a glass greenhouse, which can be an alternative when it is uncomfortable for patients to be outdoors. The lamps investigated were: halogen lamps (overhead and slide projector), white light-emitting diode (LED) lamp, red LED panel and lamps used for conventional PDT. Four of the five light sources were able to photobleach PpIX completely. For halogen light and the red LED lamp, 5000 lux could photobleach PpIX whereas 12,000 lux were needed for the white LED lamp. Furthermore, the greenhouse was suitable for daylight PDT since the effect of solar light is lowered only by 25%. In conclusion, we found four of the five light sources and the greenhouse usable for indoor daylight PDT. The greenhouse is beneficial when the weather outside is rainy or windy. Only insignificant ultraviolet B radiation (UVB) radiation passes through the greenhouse glass, so sun protection is not needed

Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis

Background: The mechanisms of cerebrospinal fluid (CSF) production by the ventricular choroid plexus (ChP) have not been fully deciphered. One prominent hypothesized mechanism is trans-epithelial water transport mediated by accumulation of solutes at the luminal ChP membrane that produces local osmotic gradients. However, this standing osmotic gradient hypothesis has not been systematically tested. Methods: To assess the plausibility of the standing gradient mechanism serving as the main driver of CSF production by the ChP, we developed a three-dimensional (3D) and a one-dimensional (1D) computational model to quantitatively describe the associated processes in the rat ChP inter-microvillar spaces and in CSF pools between macroscopic ChP folds (1D only). The computationally expensive 3D model was used to examine the applicability of the 1D model for hypothesis testing. The 1D model was employed to predict the rate of CSF produced by the standing gradient mechanism for 200,000 parameter permutations. Model parameter values for each permutation were chosen by random sampling from distributions derived from published experimental data. Results: Both models predict that the CSF production rate by the standing osmotic gradient mechanism is below 10% of experimentally measured values that reflect the contribution of all actual production mechanisms. The 1D model indicates that increasing the size of CSF pools between ChP folds, where diffusion dominates solute transport, would increase the contribution of the standing gradient mechanism to CSF production. Conclusions: The models suggest that the effect of standing osmotic gradients is too small to contribute substantially to CSF production. ChP motion and movement of CSF in the ventricles, which are not accounted for in the models, would further reduce this effect, making it unlikely that standing osmotic gradients are the main drivers of CSF production

Natively fat-suppressed 5D whole-heart MRI with a radial free-running fast-interrupted steady-state (FISS) sequence at 1.5T and 3T.

To implement, optimize, and test fast interrupted steady-state (FISS) for natively fat-suppressed free-running 5D whole-heart MRI at 1.5 tesla (T) and 3T. FISS was implemented for fully self-gated free-running cardiac- and respiratory-motion-resolved radial imaging of the heart at 1.5T and 3T. Numerical simulations and phantom scans were performed to compare fat suppression characteristics and to determine parameter ranges (number of readouts [NR] per FISS module and TR) for effective fat suppression. Subsequently, free-running FISS data were collected in 10 healthy volunteers and images were reconstructed with compressed sensing. All acquisitions were compared with a continuous balanced steady-state free precession version of the same sequence, and both fat suppression and scan times were analyzed. Simulations demonstrate a variable width and location of suppression bands in FISS that were dependent on TR and NR. For a fat suppression bandwidth of 100 Hz and NR ≤ 8, simulations demonstrated that a TR between 2.2 ms and 3.0 ms is required at 1.5T, whereas a range of 3.0 ms to 3.5 ms applies at 3T. Fat signal increases with NR. These findings were corroborated in phantom experiments. In volunteers, fat SNR was significantly decreased using FISS compared with balanced steady-state free precession (P < 0.05) at both field strengths. After protocol optimization, high-resolution (1.1 mm <sup>3</sup> ) 5D whole-heart free-running FISS can be performed with effective fat suppression in under 8 min at 1.5T and 3T at a modest scan time increase compared to balanced steady-state free precession. An optimal FISS parameter range was determined enabling natively fat-suppressed 5D whole-heart free-running MRI with a single continuous scan at 1.5T and 3T, demonstrating potential for cardiac imaging and noncontrast angiography

Recording and quantification of ultrasonic echolocation clicks from free-ranging toothed whales

Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 54 (2007): 1421-1444, doi:10.1016/j.dsr.2007.04.020.Toothed whales produce short, ultrasonic clicks of high directionality and source level to probe their environment acoustically. This process, termed echolocation, is to a large part governed by the properties of the emitted clicks. Therefore derivation of click source parameters from free-ranging animals is of increasing importance to understand both how toothed whales use echolocation in the wild and how they may be monitored acoustically. This paper addresses how source parameters can be derived from free-ranging toothed whales in the wild using calibrated multi-hydrophone arrays and digital recorders. We outline the properties required of hydrophones, amplifiers and analog to digital converters, and discuss the problems of recording echolocation clicks on the axis of a directional sound beam. For accurate localization the hydrophone array apertures must be adapted and scaled to the behavior of, and the range to, the clicking animal, and precise information on hydrophone locations is critical. We provide examples of localization routines and outline sources of error that lead to uncertainties in localizing clicking animals in time and space. Furthermore we explore approaches to time series analysis of discrete versions of toothed whale clicks that are meaningful in a biosonar context.This work was supported by a Steno Fellowship from the Danish National Science Foundation to PTM, a grant from the Carlsberg Foundation to MW with additional support to the authors from Reson, the Novo Nordisk Science Foundation, Aarhus University Research Fund, and the Oticon Foundation

Environmental effects of ozone depletion, UV radiation and interactions with climate change : UNEP Environmental Effects Assessment Panel, update 2017

Peer reviewe

A Fresh Look at Motion to Make Strides in Whole-Heart Coronary Magnetic Resonance Angiography

Magnetic resonance imaging (MRI) is an increasingly popular imaging modality in the management of cardiovascular diseases. For high-resolution anatomical imaging of the whole heart, ECG-triggering is usually used to confine the data acquisition to a quiescent period of the cardiac cycle. Due to the time consuming acquisition process, which easily exceeds comfortable breath-hold durations, the conventional approach is to image patients under free breathing. To suppress artifacts from respiratory motion, diaphragmatic navigator echoes are commonly used to only accept data acquired at end-expiration. Skilled operators can obtain excellent anatomical images with this technique but the imaging efficiency is low, the scan time unpredictable, and the planning relatively complicated. ln this dissertation, the strengths and weaknesses of existing methods for whole-heart MRI are first evaluated and then a novel technique aiming at a simplified workflow is proposed. Moreover, an automated method for image quality assessment relying on artificial intelligence is reported and leveraged in the reconstruction and analysis of whole-heart MR images. Chapter 1 of this thesis covers the motivation and prerequisites for the subsequently presented scientific work. ln Chapter 2, the conventional navigator-gated strategy is compared to a more recent self-navigated technique in which the respiratory motion is detected and corrected for using the imaging data itself, thus allowing for 100% acceptance of the acquired data. This comparison closed a gap in the contemporary scientific literature by adopting protocols from published patient studies and evaluating their performance, assessed using image quality metrics such as the visible length and the sharpness of the coronary arteries, in a cohort of healthy adult volunteers. The self-navigated technique did not provide as conspicuous coronary arteries as its navigator-gated counterpart. Nevertheless, the self-navigated technique demonstrated several important advantages, including faster and more predictable scan times, simplified planning, improved blood pool signal homogeneity, and a large field-of-view with isotropie resolution that allows for simultaneous imaging of the thoracic vasculature. ln Chapter 3, a novel, time-efficient strategy for producing motion-suppressed images is proposed and evaluated. The strategy combines existing "free-running" acquisitions that have been developed in our research group, i.e. pulse sequences that continuously acquire data irrespective of the ongoing cardiac and respiratory motion, with a novel Similarity-driven Multi-dimensional Binning Algorithm (SIMBA). The latter uses clustering of regularly acquired readouts in the superior-inferior direction to automatically identify a subset of data that was acquired in a similar motion state and thus can be reconstructed into an image with minimal motion artifact degradation. SIMBA was first tested in a proof-of-concept study including both non-contrast and contrast-enhanced free­ running scans and thereafter translated into the clinical setting at Lausanne University Hospital (CHUV) for imaging of congenital heart disease patients. ln Chapter 4, extensions of SIMBA that were tested in this patient cohort are described, enabling both improved image quality and reconstruction of multiple motion states. ln Chapter 5, a deep learning method for performing automated image quality assessment in whole-heart MRI is presented. ln particular, it was demonstrated that a convolutional neural network can be used to mimie human expert assessment of image quality. The method proved useful in several applications including comparing the image quality resulting from different strategies for extracting respiratory motion information, reducing image artifacts originating from noisy receiver coil elements, identifying the best images in dynamic datasets to facilitate the work of the reader, and regularizing undersampled inverse reconstruction problems in whole-heart MRI. ln conclusion, it was found that one of the most utilized self-navigated whole-heart techniques provide images with less conspicuous coronary arteries than the time-inefficient conventional navigator-gated approach. Moreover, it was demonstrated that the inherent similarities in the data acquired with a free-running sequence can be used to cluster said data into motion-consistent subsets, without relying on stringent physiological assumptions, using the proposed SIMBA technique. That finding paved the way for fast reconstructions of high­ resolution images of the whole heart and the great vessels. lt was also shown that information exchange between different SIMBA clusters enables improved image quality. Lastly, automated image quality assessment based on artificial intelligence proved its utility in various applications, which suggests that it may become an important tool in the development and validation of new methods in the future. Altogether, the proposed techniques may facilitate a more widespread usage of high-resolution whole-heart MRI by improving the ease-of-use. -- L'imagerie par résonance magnétique (IRM) est une modalité d'imagerie de plus en plus répandue dans la prise en charge des maladies cardiovasculaires. En imagerie anatomique cardiaque à haute résolution, l'ECG est habituellement utilisé pour acquérir des données exclusivement lors des périodes de mouvement cardiaque minimal. L'approche la plus courante consiste à imager les patients sous respiration libre, en raison du long processus d'ac quisition, qui peut aisément dépasser la durée possible d'apnée. Pour supprimer les artéfacts dus au mouvement respiratoire, seules les données acquises à la fin de l'expiration sont généralement acc eptées. Les opérateurs qualifiés peuvent obtenir d'excellentes images anatomiques avec cette technique, mais l'efficacité de l'imagerie est minime, le temps d'acquisition imprévisible et la planification compliquée. Dans cette thèse, les méthodes existantes pour l'IRM du cœur entier sont comparées, une nouvelle technique simplifiée est proposée et un moyen d'effectuer une évaluation automatisée de la qualité d'images, ainsi que ses applications, sont décrits. Le chapitre 1 de cette thèse couvre la motivation et les prérequis pour le travail scientifique présenté ultérieurement. Dans le chapitre 2, la stratégie conventionnelle dite de « navigator-gating » est comparée à une technique de « self-navigation » plus récente où le mouvement respiratoire est corrigé afin de permettre l'acceptation à 100% des données IRM acquises. La comparaison consiste à adopter des protocoles issus d'études cliniques publiées, et à évaluer leurs performances en termes de qualité d'image dans une cohorte de volontaires adultes sains. Il est montré que la qualité d'image obtenue avec la technique de self-navigation n'atteint pas le standard fixé par l'approche navigator-gating en ce qui concerne la netteté des artères coronaires. Néanmoins, la technique de self-navigation a démontré plusieurs avantages importants, notamment des temps d'acquisition plus rapides et plus prévisibles, une planification simplifiée, une meilleure homogénéité du signal sanguin et un large champ de vue avec une résolution isotrope qui permet d'imager simultanément le réseau vasculaire thoracique. Dans le chapitre 3, une nouvelle stratégie de production d'images anatomiques est présentée et étudiée . Cette stratégie combine des acquisitions dites « free-running » déjà existantes, c'est-à-dire des séquences qui acquièrent continuellement des données indépendamment du mouvement cardiaque et respiratoire en cours, et la nouvelle technique « Similarity-driven Multi-dimensional Binning Algorithm (SIMBA) » qui identifie automatiquement les données acquises dans un état de mouvement physiologique similaire. Les données acquises peuvent alors être reconstruites pour former une image contenant très peu d'artéfacts de mouvement. La technique SIMBA est tout d'abord testée lors d' une étude de validation, avec ou sans injection de produit de contraste, puis traduite dans l'environnement clinique du Centre hospitalier universitaire vaudois pour l'imagerie des patients atteints de cardiopathie congénitale. Dans le chapitre 4, des développements ultérieurs ont permis d'améliorer la qualité des images SIMBA et de reconstruire plusieurs états de mouvement au lieu d'un seul. Dans le chapitre 5, une méthode basée sur l'apprentissage profond permettant une évaluation automatisée de la qualité d'image en IRM du cœur entier est présentée. En particulier, il est démontré qu'un réseau de neurones convolutifs peut imiter l'évaluation de la qualité d'image faite par des experts humains. De plus, ce modèle s'est avéré être utile pour plusieurs applications, plus précisément pour comparer différentes stratégies d'extraction de l'information respiratoire, pour réduire l'influence des éléments d'antenne apportant du bruit aux images, pour identifier les meilleures images dans des séries dynamiques et pour régulariser des problèmes de reconstruction inverse. En conclusion, il a été constaté que l'une des techniques de self-navigation du cœur entier les plus utilisées fournit des images avec des artères coronaires moins visibles que l'approche conventionnelle de navigator­ gating, mais que self-navigation est beaucoup plus efficace. La nouvelle technique SIMBA simplifie l'IRM du cœur entier à haute résolution. Son développement ultérieur pourrait être facilité par l'évaluation automatisée de la qualité d'image. En tout, ce travail de doctorat s'inscrit dans une démarche de démocratisation de l'IRM du cœur entier

RNA analysis of tape strips to rule out melanoma in lesions clinically assessed as cutaneous malignant melanoma

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