New MRI Techniques for Nanoparticle Based Functional and Molecular Imaging

Although in clinical use for several decades, magnetic resonance imaging: MRI) is undergoing a transition from a qualitative anatomical imaging tool to a quantitative technique for evaluating myriad diseases. Furthermore, MRI has made great strides as a potential tool for molecular imaging of cellular and tissue biomarkers. Of the candidate contrast agents for molecular MRI, the excellent bio-compatibility and adaptability of perfluorocarbon nanoparticles: PFC NP) has established these agents as a potent targeted imaging agent and as a functional platform for non-invasive oxygen tension sensing. Direct readout and quantification of PFC NP can be achieved with fluorine: 19F) MRI because of the unique 19F signal emanating from the core PFC molecules. However, the signal is usually limited by the modest accumulated concentrations as well as several special NMR considerations for PFC NP, which renders 19F MRI technically challenging in terms of detection sensitivity, scan time, and image reconstruction. In the present dissertation, some of the pertinent NMR properties of PFC NP are investigated and new 19F MRI techniques developed to enhance their performance and expand the biomedical applications of 19F MRI with PFC NP. With the use of both theoretical and experimental methods, we evaluated J-coupling modulation, chemical shift and paramagnetic relaxation enhancement of PFC molecules in PFC NP. Our unique contribution to the technical improvement of 19F MRI of small animal involves:: 1) development of general strategies for RF 1H/19F coil design;: 2) design of novel MR pulse sequences for 19F T1 quantification; and: 3) optimization of imaging protocols for distinguishing and visualizing multiple PFC components: multi-chromatic 19F MRI). The first pre-clinical application of our novel 19F MRI techniques is blood vessel imaging and rapid blood oxygen tension measurement in vivo. Blood vessel anatomy and blood oxygen tension provide pivotal physiological information for routine diagnosis of cardiovascular disease. Using our novel Blood: flow)-Enhanced-Saturation-Recovery: BESR) sequence, we successfully visualized reduced flow caused by thrombosis in carotid arteries and jugular veins, and we quantified the oxygen tension in the cardiac ventricles of the mouse. The BESR sequence depicted the expected oxygenation difference between arterial and venous blood and accurately registered the response of blood oxygen tension to high oxygen concentration in 100% oxygen gas. This study demonstrated the potential application of PFC NP as a blood oxygen tension sensor and blood pool MR contrast agent for angiography. Another pre-clinical application investigated was functional kidney imaging with 19F MRI of circulating PFC NP. Conventional functional kidney imaging typically calls for the injection of small molecule contrast agents that may be nephrotoxic, which raises concerns for their clinical applications in patients with renal insufficiency. We demonstrated that our 19F MRI technique offers a promising alternative functional renal imaging approach that generates quantitative measurement of renal blood volume and intrarenal oxygenation. We successfully mapped the expected heterogeneous distribution of renal blood volume and confirmed the presence of an oxygenation gradient in healthy kidneys. We validated the diagnostic capability of 19F MRI in a mouse model of acute ischemia/reperfusion kidney injury. We also employed 19F MRI as a tool to test the therapeutic efficacy of a new nanoparticle-based drug, i. e. PPACK: D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone) PFC NP, which was postulated to inhibit microvascular coagulation during acute kidney injury. Based on our preliminary 19F MRI findings, we observed that PPACK PFC NP effectively reduced coagulation in our animal model, as evidenced by lesser accumulation of particles trapped by the clotting process. This finding suggests the potential for 19F MRI to be used as a drug monitoring tool as well in common medical emergencies such as acute kidney failure

Phoenix dactylifera L. sap enhances wound healing in Wistar rats : Phytochemical and histological assessment

Acknowledgment Financial support of the Tunisian Ministry of Higher Education and Scientific Research is gratefully acknowledged.Peer reviewedPostprin

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 140

This bibliography lists 306 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1975

Considerations of education in the field of biophotonics in engineering: the experience of the subject Fundamentals of Biophotonics

Education in the field of photonics is usually somehow complex due to the fact that most of the programs include just a few subjects on the field, apart from specific Master programs in Photonics. There are also specific doctorate programs dealing with photonics. Apart from the problems shared with photonics in education in general, biophotonics specifically needs an interdisciplinary approach between biomedical and technical or scientific fields. In this work, we present our education experience in teaching the subject Fundamentals of Biophotonics, intended preferentially to engineering Bachelor and Master degrees students, but also to science and medicine students. First it was necessary to join a teaching group coming from the scientific technical and medical fields, working together in the subject. This task was easier as our research group, the Applied Optical Techniques group, had previous contacts and experience in working with medicine professors and medical doctors at hospitals. The orientation of the subject, intended for both technical and medical students, has to be carefully selected. All this information could be employed by other education institutions willing to implement studies on biomedical optics.This work has been partially supported by the project “New active phases in transition metals and rare earth nano-oxides stabilized at high pressure” (MAT2015-69508-P) of the Spanish Ministry of Economy and Competitiveness, cofunded by FEDER funds, and by the San Cándido Foundation

Measurement of proteinuria

In pregnancy, there is a focus on measurement of proteinuria as it has been regarded as critical to the diagnosis of pre-eclampsia, the most dangerous of the hypertensive disorders of pregnancy. However, it is increasingly recognised that proteinuria is not essential for the diagnosis of pre-eclampsia, which can be based on other end-organ complications (such as elevated liver enzymes). Although heavy proteinuria has been linked with an increased risk of stillbirth in a ‘signs and symptoms only’ model of maternal risk (i.e., miniPIERS), we lack the ability to identify a level of proteinuria above which maternal and/or perinatal risk is heightened. Therefore, at present, we rely on the detection of proteinuria that exceeds what is normally excreted by healthy pregnant women. Proteinuria detection methods are also a matter of keen debate, with all available methods having advantages and disadvantages.Publisher PD

Three Pillars of Novel Nonthermal Food Technologies:Food Safety, Quality, and Environment

This review gives an overview of the impact of novel nonthermal food technologies on food safety, on quality, and on the environment. It confirms that research in this field is mainly focused on analyzing microbial and/or chemical aspects of food safety. However, recent research shows that in spite of various food safety benefits, some negative (quality oriented) features occur. Finally, this paper shows the necessity of analyzing the environmental dimension of using these technologies

Age estimation of blood stains using different analytical techniques and the in-situ identification of proteins using BCA

The issue of establishing a correct timeline in terms of body fluids has always been an important aspect in any forensic investigation. The techniques currently being used have all proved to work quite well but have certain limitations. One of the main problems with these techniques is their invasiveness to the sample in question. This is a major problem as, in most cases, the sample analysed is quite small and the destruction of it via the use of one technique can limit it being used for other key experiments, all of which are important for an investigation. In this project, the aim was to present a collection of techniques that have been proven to be non-invasive on samples and at the same time, provide key information regarding the identity of the sample in estimating the age. Techniques such as Raman Spectroscopy, Colorimetry and Small Angle X-Ray Scattering were used to establish the identity and estimate the age of a stain. Results were obtained which showed that Raman Spectroscopy and Colorimetry provided the most useful information regarding the body fluid used. Another aspect of this project was to develop a technique that could be used to identify the presence of proteins on crime scenes. Bicinchoninic Acid (BCA) was used for this part of the project along with copper sulphate. The results obtained showed that the presence of proteins could be identified but the results were not specific enough to describe what type of protein was being detected. More work needs to be done on this part as it has potential to be modified and become human specific by adding fluorescent probes that are human protein (skin keratin) specific and therefore can be used as an identifying tool in terms of evidence collection and processing it for DNA profiling

Answers in a flash; optical analysis of exocytosis in human cultured endothelial cells

Endothelial cells line all of our blood vessels. They monitor and respond to signals generated during injury, infection and disease by releasing a wide range of molecules that regulate blood flow, coagulation, inflammatory responses and vessel growth. Protein mediators are released by exocytosis of intracellular organelles, and a major trigger for this type of secretion is an increase in intracellular free calcium ion concentration ([Ca2+]i). Mitochondria are thought to influence Ca2+ homeostasis through local Ca2+ buffering. Due to a lack of sensitive and time-resolved assays for endothelial exocytosis little is known about the precise relationship between Ca2+-signalling and exocytosis, and the influence of Ca2+ buffering by mitochondria. Using fluorescence and biochemical techniques I have investigated the relationship between secretagogue-evoked Ca2+-signalling and the influence of mitochondrial function on the exocytosis of two distinct organelle populations in cultures of Human Umbilical Vein Endothelial Cells (HUVEC); 1) the Weibel-Palade body (WPB) the main storage organelle for pro-coaguland and inflammatory mediators, and 2) the non-WPB, a non-stored and morphologically distinct organelle that can contain a range of inflammatory and anti-coagulant molecules. These two distinct organelle populations were labeled for fluorescence microscopy by targeted expression of chimeras of green (EGFP) or red (mRFP) fluorescent proteins in living HUVEC. Exocytosis was evoked by both physiological and pharmacological secretogogues that increase [Ca2+]i. The times of exocytosis of individual organelles were monitored by flashes of light from granule EGFP, produced by pH changes within the organelle upon fusion. In the same experiments, [Ca2+]i and intra-mitochondrial Ca2+ concentration ([Ca2+]m) were monitored using fluorescent Ca2+-indicators. The data obtained has defined more precisely the relationship between agonist-evoked changes in [Ca2+]i and secretory vesicle exocytosis in HUVEC. These studies will contribute to a better understanding of the processes that regulate secretion of biomolecules from the endothelium

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 127, April 1974

This special bibliography lists 279 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1974

Aerospace Medicine and Biology: A continuing bibliography (supplement 249)

This bibliography lists 311 reports, articles and other documents introduced into the NASA scientific and technical information system in August 1983