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      Contrast Agents Delivery: An Up-to-Date Review of Nanodiagnostics in Neuroimaging

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          Abstract

          Neuroimaging is a highly important field of neuroscience, with direct implications for the early diagnosis and progression monitoring of brain-associated diseases. Neuroimaging techniques are categorized into structural, functional and molecular neuroimaging, each possessing advantages and disadvantages in terms of resolution, invasiveness, toxicity of contrast agents and costs. Nanotechnology-based approaches for neuroimaging mostly involve the development of nanocarriers for incorporating contrast agents or the use of nanomaterials as imaging agents. Inorganic and organic nanoparticles, liposomes, micelles, nanobodies and quantum dots are some of the most studied candidates for the delivery of contrast agents for neuroimaging. This paper focuses on describing the conventional modalities used for imaging and the applications of nanotechnology for developing novel strategies for neuroimaging. The aim is to highlight the roles of nanocarriers for enhancing and/or overcome the limitations associated with the most commonly utilized neuroimaging modalities. For future directions, several techniques that could benefit from the increased contrast induced by using imaging probes are presented.

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          Most cited references148

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          Liposomes and polymersomes: a comparative review towards cell mimicking

          Minimal cells: we compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications). Cells are integral to all forms of life due to their compartmentalization by the plasma membrane. However, living organisms are immensely complex. Thus there is a need for simplified and controllable models of life for a deeper understanding of fundamental biological processes and man-made applications. This is where the bottom-up approach of synthetic biology comes from: a stepwise assembly of biomimetic functionalities ultimately into a protocell. A fundamental feature of such an endeavor is the generation and control of model membranes such as liposomes and polymersomes. We compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications) and which aspects have been studied and developed with each type and update the current development in the field.
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            Nanobodies as therapeutics: big opportunities for small antibodies.

            Members of the Camelidae (including camels and llamas) produce, in addition to conventional antibodies (Ab), a unique type of Ab that lacks light chains. The variable antigen-binding domains derived from these Ab are named 'nanobodies' (Nbs). Nbs exert high specificity and affinity and, when properly selected, are more stable than conventional Ab. Furthermore, their toxicity and immunogenicity are both low. They are easy to produce and their modularity makes them amenable for the generation of multivalent complexes. In this review, we discuss how Nbs are being explored as therapeutics in many fields of medicine, including oncology, inflammatory, infectious and neurological diseases, and imaging. In addition, we highlight their potential for use in the diagnosis and monitoring of diseases. Finally, we provide an extended overview of Nbs that are, or have been, involved in clinical trials.
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              X-ray phase-contrast imaging: from pre-clinical applications towards clinics.

              Phase-contrast x-ray imaging (PCI) is an innovative method that is sensitive to the refraction of the x-rays in matter. PCI is particularly adapted to visualize weakly absorbing details like those often encountered in biology and medicine. In past years, PCI has become one of the most used imaging methods in laboratory and preclinical studies: its unique characteristics allow high contrast 3D visualization of thick and complex samples even at high spatial resolution. Applications have covered a wide range of pathologies and organs, and are more and more often performed in vivo. Several techniques are now available to exploit and visualize the phase-contrast: propagation- and analyzer-based, crystal and grating interferometry and non-interferometric methods like the coded aperture. In this review, covering the last five years, we will give an overview of the main theoretical and experimental developments and of the important steps performed towards the clinical implementation of PCI.
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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                03 April 2019
                April 2019
                : 9
                : 4
                : 542
                Affiliations
                [1 ]Emergency University Hospital, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; daniel.teleanu@ 123456umfcd.ro
                [2 ]Faculty of Engineering in Foreign Languages, Politehnica University of Bucharest, 060042 Bucharest, Romania; cristina.chircov@ 123456yahoo.com
                [3 ]Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, 011061 Bucharest, Romania; grumezescu@ 123456yahoo.com
                [4 ]ICUB—Research Institute of University of Bucharest, University of Bucharest, 36-46 M. Kogalniceanu Blvd., Bucharest 050107, Romania
                [5 ]“Victor Gomoiu” Clinical Children’s Hospital, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; raluca.teleanu@ 123456umfcd.ro
                Author notes
                [* ]Correspondence: avolceanov@ 123456yahoo.co.uk or adrian.volceanov@ 123456upb.ro ; Tel.: +4021-402-39-97
                Author information
                https://orcid.org/0000-0003-3036-094X
                https://orcid.org/0000-0002-7668-861X
                Article
                nanomaterials-09-00542
                10.3390/nano9040542
                6523665
                30987211
                78ad8f3a-c0ce-4f69-8ed1-a45ea221e4a6
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 March 2019
                : 29 March 2019
                Categories
                Review

                neuroimaging,neuroscience,nanotechnology,imaging,contrast agents

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