The near-infrared autofluorescence fingerprint of the brain

This is the peer reviewed version of the following article: Lifante, J, del Rosal, B, Chaves-Coira, I, Fernández, N, Jaque, D, Ximendes, E. The near-infrared autofluorescence fingerprint of the brain. J. Biophotonics. 2020; 13:e202000154, which has been published in final form at https://doi.org/10.1002/jbio.202000154. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe brain is a vital organ involved in mostof the central nervous system disorders.Their diagnosis and treatment require fast,cost-effective, high-resolution and high-sensitivity imaging. The combinationof a new generation of luminescent nanoparticles and imaging systems work-ing in the second biological window (near-infrared II [NIR-II]) is emerging asa reliable alternative. For NIR-II imaging to become a robust technique at thepreclinical level, full knowledge of the NIR-II brain autofluorescence, responsi-ble for the loss of image resolution and contrast, is required. This work demon-strates that the brain shows a peculiar infrared autofluorescence spectrumthat can be correlated with specific molecular components. The existence ofparticular structures within the brain with well-defined NIR autofluorescencefingerprints is also evidenced, opening the door to in vivo anatomical imaging.Finally, we propose a rational selection of NIR luminescent probes suitable forlow-noise brain imaging based on their spectral overlap with brainautofluorescenceComunidad de Madrid, Grant/AwardNumber: B2017/BMD-3867RENIMCM;European Cooperation in Science andTechnology, Grant/Award Number:CA17140; Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal, Grant/Award Number:IMP18_38(2018/0265); Horizon 2020 Framework Programme, Grant/AwardNumber: 801305; Instituto de Salud CarlosIII, Grant/Award Number: PI16/00812;Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number:FJC2018-036734-I; Ministerio deEconomía y Competitividad, Grant/AwardNumbers: MAT2016-75362-C3-1-R,MAT2017-83111R, MAT2017-85617-

Reliable and remote monitoring of absolute temperature during liver inflammation via luminescence-lifetime-based nanothermometry

Temperature of tissues and organs is one of the first parameters affected by physiological and pathological processes, such as metabolic activity, acute trauma, or infection-induced inflammation. Therefore, the onset and development of these processes can be detected by monitoring deviations from basal temperature. To accomplish this, minimally invasive, reliable, and accurate measurement of the absolute temperature of internal organs is required. Luminescence nanothermometry is the ideal technology for meeting these requirements. Although this technique has lately undergone remarkable developments, its reliability is being questioned due to spectral distortions caused by biological tissues. In this work, how the use of bright Ag2S nanoparticles featuring temperature-dependent fluorescence lifetime enables reliable and accurate measurement of the absolute temperature of the liver in mice subjected to lipopolysaccharide-induced inflammation is demonstrated. Beyond the remarkable thermal sensitivity (≈ 3% °C–1 around 37 °C) and thermal resolution obtained (smaller than 0.3 °C), the results included in this work set a blueprint for the development of new diagnostic procedures based on the use of intracorporeal temperature as a physiological indicatorY.S. J.L., and I.Z.-G. contributed equally to this work. This work was supported by the Spanish Ministerio de Ciencia under project PID2019-106211RB-I00 and Ministerio de Economía y Competitividad under project MAT2017-83111R, by the Comunidad Autónoma de Madrid (B2017/BMD-3867 RENIM-CM), and co-financed by the European Structural and Investment fund. Additional funding was provided by the European Union’s Horizon 2020 FET Open program (Grant Agreement No. 801305, NanoTBTech), and also by COST action CA17140. Y.S. acknowledges a scholarship from the China Scholarship Council (No. 201806870023). I.Z.-G. thanks UCM-Santander for a predoctoral contract (CT63/19-CT64/19). M.F was funded by a research contract from the Community of Madrid (PEJ-2018-AI/SAL-11315). E.X. is grateful for a Juan de la Cierva Formación scholarship (FJC2018-036734-I). J.L. is grateful for FPI scholarship PID2019-106211RB-100. A. B. acknowledges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-1401

Early in vivo detection of denervation-induced atrophy by luminescence transient nanothermometry

Denervation induces skeletal muscle atrophy due to the loss of control and feedback with the nervous system. Unfortunately, muscle atrophy only becomes evident days after the denervation event when it could be irreversible. Alternative diagnosis tools for early detection of denervation-induced muscle atrophy are, thus, required. In this work, we demonstrate how the combination of transient thermometry, a technique already used for early diagnosis of tumors, and infrared-emitting nanothermometers makes possible the in vivo detection of the onset of muscle atrophy at short (<1 day) times after a denervation event. The physiological reasons behind these experimental results have been explored by performing three dimensional numerical simulations based on the Pennes' bioheat equation. It is concluded that the alterations in muscle thermal dynamics at the onset of muscle atrophy are consequence of the skin perfusion increment caused by the alteration of peripheral nervous autonomous system. This work demonstrates the potential of infrared luminescence thermometry for early detection of diseases of the nervous system opening the venue toward the development of new diagnosis toolsComunidad de Madrid, Grant/Award Number: S2017/BMD-3867 RENIM-CM; COST action CA17140 (Nano2Clinic); European Structural and Investment Fund and the Ministerio de Economía y Competitividad-MINECO, Grant/Award Number: PID2019-106211RB-I00; Juan de la Cierva scholarship, Grant/Award Number: IJC2020-045229-

Crimean-Congo haemorrhagic fever (CCHF) virus-specific antibody detection in blood donors, Castile-León, Spain, summer 2017 and 2018

BackgroundCrimean-Congo haemorrhagic fever virus (CCHFV) is considered an emerging or even a probable re-emerging pathogen in southern Europe. Presence of this virus had been reported previously in Spain in 2010.AimWe aimed to evaluate the potential circulation of CCHFV in western Spain with a serosurvey in asymptomatic adults (blood donors).MethodsDuring 2017 and 2018, we conducted a CCHFV serosurvey in randomly selected asymptomatic blood donors from western Spain. Three assays using specific IgG antibodies against CCHFV were performed: the VectoCrimea ELISA test, an in-house ELISA and indirect immunofluorescence (EuroImmun) test with glycoprotein and nucleoprotein.ResultsA total of 516 blood donors participated in this cross-sectional study. The majority of the study participants were male (68.4%), and the mean age was 46.3 years. Most of the participants came from rural areas (86.8%) and 68.6% had contact with animals and 20.9% had animal husbandry practices. One in five participants (109/516, 21.1%) were engaged in at-risk professional activities such as agriculture and shepherding, slaughtering, hunting, veterinary and healthcare work (mainly nursing staff and laboratory technicians). A total of 15.3% of the participants were bitten by ticks in the days or months before the date of sampling. We detected anti-CCHFV IgG antibodies with two diagnostic assays in three of the 516 individuals and with one diagnostic assay in six of the 516 individuals.ConclusionSeroprevalence of CCHFV was between 0.58% and 1.16% in Castile-León, Spain. This is the first study in western Spain that showed circulation of CCHFV in healthy people.This study was supported by the Institute of Health Carlos III, ISCIII, Spain (www.isciii.es), grants: RICET RD16/0027/0018 (AM) and RD16/0003/0003 (MPSS), DTS16/00207 (AM), PI16/01784 (PFS), European Union co-financing by FEDER (Fondo Europeo de Desarrollo Regional) ‘Una manera de hacer Europa’.S