The Boston University Photonics Center annual report 2014-2015

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2014-2015 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $18.6M in new research grants/contracts. Faculty and staff also expanded their efforts in education and training, and were awarded two new National Science Foundation– sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Advanced Materials by Design for the 21st Century at our annual symposium. We continued to support the National Photonics Initiative, and are a part of a New York–based consortium that won the competition for a new photonics- themed node in the National Network of Manufacturing Institutes. Highlights of our research achievements for the year include an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, continued support of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Catherine Klapperich, a new award for Personalized Chemotherapy Through Rapid Monitoring with Wearable Optics led by Assistant Professor Darren Roblyer, and a new award from DARPA to conduct research on Calligraphy to Build Tunable Optical Metamaterials led by Professor Dave Bishop. We were also honored to receive an award from the Massachusetts Life Sciences Center to develop a biophotonics laboratory in our Business Innovation Center

The Boston University Photonics Center annual report 2014-2015

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2014-2015 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $18.6M in new research grants/contracts. Faculty and staff also expanded their efforts in education and training, and were awarded two new National Science Foundation– sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Advanced Materials by Design for the 21st Century at our annual symposium. We continued to support the National Photonics Initiative, and are a part of a New York–based consortium that won the competition for a new photonics- themed node in the National Network of Manufacturing Institutes. Highlights of our research achievements for the year include an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, continued support of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Catherine Klapperich, a new award for Personalized Chemotherapy Through Rapid Monitoring with Wearable Optics led by Assistant Professor Darren Roblyer, and a new award from DARPA to conduct research on Calligraphy to Build Tunable Optical Metamaterials led by Professor Dave Bishop. We were also honored to receive an award from the Massachusetts Life Sciences Center to develop a biophotonics laboratory in our Business Innovation Center

Peripheral Blood and Salivary Biomarkers of Blood-Brain Barrier Permeability and Neuronal Damage:Clinical and Applied Concepts

International audienceWithin the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings

Watch your head: brain neurophysiology and contact sports

In the world of contact sports there is rising concern about the long-term effects of sport participation on athletes’ brains. Apart from concussions, the repetitive subconcussive head impacts (RSHI) in sports have been suggested to be detrimental for brain health. RSHI in football are thought to be linked with the onset of neurodegenerative diseases, like Chronic Traumatic Encephalopathy and Alzheimer’s disease. However, to understand how and why the athletes’ brains might suffer in the long-term, we should first understand the acute brain changes caused by the potential risk factors for brain damage (concussive and sub-concussive impacts). The experimental studies of this PhD thesis aim to investigate the acute effects of heading, the main source of RSHI in football, on the brain functions of athletes, by using a mixture of sensitive neuroscientific modalities. Secondary data is used in this thesis for method development and to examine the broader problem posed by sport-related head impact. Chapter 1 expands on the aims of the thesis. Chapter 2 presents the current state of the literature on RSHI. Chapter 3 includes a scoping review of the literature on biofluid markers use to assess the effects of RSHI highlighting the high heterogeneity of the existing studies and providing guidelines for future studies. Chapter 4 includes an investigation of the injury characteristics and prognosis of sport-related traumatic brain injury (TBI). It highlights the seriousness of sport-related TBI and specifically sport-related mTBI, whose remaining effects can potentially be worsened by the burden of RSHI during play. Chapter 5 investigated the effects of RSHI on balance in various ways, providing no evidence of an effect, while chapter 6 provides evidence for associative memory changes caused by heading. The following chapters (7 & 8) attempted to further examine the alterations in cognitive functioning post heading and present the first EEG evidence that the cognitive functions of attention, memory and learning are acutely affected by RSHI. After showing that RSHI affect mainly association learning and attention processes and not affect response inhibition, motor control and motor learning, chapter 9 aimed to examine the replicability of RSHI effects on motor cortex inhibition, providing evidence of no effect. The outcome of this thesis is that RSHI have detrimental effects to athletes’ cognition, mainly in the functions of learning and attention, while motor control appears to remain intact

Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing “omics”-based, diagnostic tests to help influence therapies

Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group

Abstract: The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significant, and the heterogeneity of TBI patients and the relatively small sample sizes of most current neuroimaging studies is a major challenge for scientific advances and clinical translation. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Adult moderate/severe TBI (AMS-TBI) working group aims to be a driving force for new discoveries in AMS-TBI by providing researchers world-wide with an effective framework and platform for large-scale cross-border collaboration and data sharing. Based on the principles of transparency, rigor, reproducibility and collaboration, we will facilitate the development and dissemination of multiscale and big data analysis pipelines for harmonized analyses in AMS-TBI using structural and functional neuroimaging in combination with non-imaging biomarkers, genetics, as well as clinical and behavioral measures. Ultimately, we will offer investigators an unprecedented opportunity to test important hypotheses about recovery and morbidity in AMS-TBI by taking advantage of our robust methods for large-scale neuroimaging data analysis. In this consensus statement we outline the working group’s short-term, intermediate, and long-term goals

Developing neuroimaging biomarkers of blast-induced traumatic brain injury

In the past two decades, the awareness of the physical and emotional effects and sequalae of traumatic brain injuries (TBI) has grown considerably, especially in the case of soldiers returning from their deployment in Iraq and Afghanistan, after sustaining blast-induced TBI (bTBI). While the understanding of bTBI and how it compares to civilian non-blast TBI is essential for proper prevention, diagnosis and treatment, it is currently limited, especially in human in-vivo studies. Developing neuroimaging biomarkers of bTBI is key in understanding primary blast injury mechanism. I therefore investigated the patterns of white matter and grey matter injuries that are specific to bTBI and aren¶t commonl\ seen in civilians Zho suffered from head trauma using advanced neuroimaging techniques. However, because of significant methodological issues and limitations, I developed and tested a new pipeline capable of running the analysis of white matter abnormalities in soldiers, called subject-specific diffusion segmentation (SSDS). I also used standard methodologies to investigate changes at the level of the grey matter structures, and more particularly the limbic system. Finally, I trained a machine learning algorithm that builds decision trees with the aim of classifying between patients with TBI and controls, and between different TBI mechanisms as an example of what could potentially be applied in the context of bTBI. I found three main neuroimaging biomarkers specific to bTBI. The first one is a microstructural white matter abnormality at the level of the middle cerebellar peduncle, characterized by a decrease of diffusivity measures. The second is also a decrease in diffusivity properties, at the level of the white matter boundary, and the third one is a loss of hippocampal volume, with no association to post-traumatic stress disorder. Finally, I demonstrated that SSDS can be used in tandem with a machine learning algorithm for potential diagnosis of TBI with high accuracy. These findings provide mechanistic insights into bTBI and the effect of primary blast injuries on the human brain. This work also identifies important neuroimaging biomarkers that might facilitate prevention and diagnosis in soldiers who suffered from bTBI.Open Acces

Systematic review of in-vivo neuro magnetic resonance spectroscopy for the assessment of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a trauma and stressor-related disorder that results in complex somatic, cognitive, affective and behavioural effects, after exposure to traumatic event(s). Conventional imaging (T1 and T2 weighted magnetic resonance imaging) has little to offer in the way of diagnosis of mental health conditions such as PTSD and there is currently no objective diagnostic test available. Magnetic resonance spectroscopy (MRS) allows for non-invasive measurement of metabolites and neurochemicals in the brain using a conventional MRI scanner and offers the potential to predict, diagnose and monitor PTSD. This systematic review summarises the results of 24 MRS studies, performed between 1998 and 2017, to measure neurochemical differences, occurring as a consequence of PTSD. The most consistent finding in subjects with PTSD is lower N-acetylaspartate levels in the hippocampus and anterior cingulate cortex, with and without atrophic change. More recent studies, using more advanced techniques and modern hardware, have shown evidence of glutamatergic dysfunction and differences in gamma-aminobutyric acid levels in the brain of patients with PTSD. Conflicting results have been reported in choline-containing metabolites and there is emerging evidence of glutathione being affected. Myo-inositol and creatine are unchanged in the majority of studies

Tehohoitopotilaiden neuromonitorointi

In critical illness the risk of neurological insults is high, whether because of the illness itself, or as a treatment complication. As a result, the length of hospital stay and the risk of both further morbidity and mortality are all roughly doubled. One of the major challenges is the inability to monitor a sedated, mechanically ventilated patient’s neurological symptoms during intensive care treatment, due to a lack of reliable methods. The aims of this thesis research were to identify and test potential non-invasive methods, which would be predictive of neurological outcome, showing potential as neuromonitoring methods of critical care patients unable to self-report. As a guiding theme, all tested methods could be applied to actual critical care with relative ease. Patients were included from two groups with a notably high incidence of neurological complications, namely acute liver failure patients with hepatic encephalopathy (I), and aortic surgery patients operated during hypothermic circulatory arrest (II). The first group included 20 patients, and the latter 30 patients. Late mortality and quality of life was assessed for the aortic surgery patients (III), and the postoperative development of certain blood biomarkers (IV). The tested non-invasive neuromonitoring methods included electroencephalogram (EEG) variables from frontal or fronto-temporal abbreviated monitoring, frontal near-infrared spectroscopy, transcranial Doppler ultrasound measurements of the intracranial blood flow, and finally biomarkers. The last included established biomarkers with an association with neurological complications, namely neuron-specific enolase, and protein S100β, and several interesting biomarkers normally associated with tumours and pancreatitis. Of the tested methods, the frontal EEG variables showed greatest promise, but the addition of the temporal channels did not increase sensitivity. Spectral EEG variables were predictive of the stage of hepatic encephalopathy (I), while a novel EEG variable called wavelet subband entropy was predictive of neurological outcome (I). The hemispheric asymmetry of frontal EEG was reasonably predictive of neurological outcome after aortic surgery (II). None of the other tested methods were predictive of outcome (I, II, IV), except protein S100β, which was significantly higher in the poor outcome group 48 to 72 hours after hypothermic circulatory arrest (II). The quality of life of aortic surgery patients was good after 5 to 8 years, and comparable with the general population of chronically ill patients (III). The aim of this explorative research was to identify and test non-invasive neuromonitoring methods, suitable for use in critical care. Based on the results, frontal EEG variables are promising and predict the grade of hepatic encephalopathy and neurological outcome. The other tested methods were not predictive of neurological outcome. The long-term quality of life of aortic surgery patients is very good, despite the high risk for neurological complications.Kriittisissä sairauksissa neurologisen komplikaation riski on suuri, sekä itse kriittisen sairauden että varsinaisen hoidon seurauksena. Haittatapahtuman johdosta sairaalahoidon kesto sekä sairastuvuuden ja kuolleisuuden riskit kaksinkertaistuvat. Yksi suurimmista haasteista on luotettavien menetelmien puute, joilla voitaisiin arvioida mekaanisen hengitystuen varassa olevan ja rauhoittavia lääkkeitä saavan potilaan neurologisia oireita tehohoidon aikana. Tämän väitöskirjatyön tarkoituksena oli tunnistaa ja testata lupaavia ei-kajoavia menetelmiä, jotka ennustaisivat neurologista lopputulosta, ja jotka soveltuisivat kriittisesti sairaan tehohoitopotilaan neuromonitorointiin. Kantavana teemana kaikki testatut menetelmät voitaisiin soveltaa kliiniseen työhön suhteellisen helposti. Potilaita kerättiin kahteen ryhmään, joissa neurologisten komplikaatioiden esiintyvyys on huomattavan suuri. Ensimmäinen ryhmä käsitti akuuttia maksan vajaatoimintaa ja hepaattista enkefalopatiaa sairastavat potilaat (I), toinen hypotermisen verenkierron pysäytyksen aikana rinta-aortan leikkauksen läpikäyvät potilaat (II). Ensimmäiseen ryhmään kuului 20 potilasta, jälkimmäiseen 30 potilasta. Aorttaleikatuilta potilailta arvioitiin myös elämänlaatua sekä myöhäiskuolleisuutta (III), lisäksi tiettyjen biomerkkiaineiden aorttaleikkauksen jälkeistä kehitystä ja soveltuvuutta neuromonitorointiin arvioitiin yhdessä osatyössä (IV). Tutkimuksessa arvioituihin ei-kajoaviin neuromonitorointimenetelmiin lukeutuivat otsa- ja ohimolohkon elektroenkefalografia (EEG), lähi-infrapunaspektroskopia, transkraniaalinen Doppler-ultraäänimittaus sekä verestä mitattavat biomerkkiaineet. Biomerkkiaineet kattoivat sekä vakiintuneita aivovauriota heijastavia merkkiaineita (hermostoperäinen enolaasi, proteiini S100β) että useita mielenkiintoisia merkkiaineita, jotka liittyvät kasvaintauteihin ja haimatulehdukseen. Testatuista menetelmistä otsalohkon EEG muuttujat olivat lupaavia, mutta ohimolohkon EEG lisääminen ei parantanut menetelmien herkkyyttä. EEG spektrimuuttujat ennustivat hepaattisen enkefalopatian astetta (I) luotettavasti, kun taas kokeellinen EEG-muuttuja (aalloke-alitaajuuden entropia) ennusti luotettavasti neurologista lopputulosta akuutin maksan vajaatoimintaa sairastavilla potilailla (I). Otsalohkon aivopuoliskojen EEG-rekisteröinnin hetkellinen epäsymmetria ennusti kohtalaisella tarkkuudella neurologisten päätetapahtumien esiintymisen aorttaleikatuilla potilailla (II). Muut testatut menetelmät eivät ennustaneet neurologista lopputulemaa (I, II, IV), paitsi proteiini S100β, joka oli merkittävästi korkeampi 48–72 tuntia leikkauksen jälkeen niillä potilailla, joiden neurologinen toipuminen oli huono (IV). Aorttaleikattujen potilaiden elämänlaatu oli hyvä 5–8 vuotta leikkauksen jälkeen ja verrattavissa kroonisesti sairaan väestön elämänlaatuun (III). Tämän kartoittavan tutkimuksen tarkoituksena oli tunnistaa ja testata ei-kajoavia neuromonitorointimenetelmiä, jotka soveltuvat tehohoitoon. Tulosten perusteella otsalohkon EEG-muuttujat ennustavat hepaattisen enkefalopatian astetta sekä potilaan neurologista toipumista. Muut testatut menetelmät eivät ennustaneet neurologista toipumista luotettavasti. Aorttaleikattujen potilaiden pitkäaikainen (5–8 vuoden) terveyteen liittyvä elämänlaatu on erittäin hyvä, vaikka leikkaukseen liittyy korkea aivovaurion riski