دورية أكاديمية
أعرض في EDS

Neuron labeling with rhodamine-conjugated Gd-based MRI contrast agents delivered to the brain via focused ultrasound.

التفاصيل البيبلوغرافية
العنوان: Neuron labeling with rhodamine-conjugated Gd-based MRI contrast agents delivered to the brain via focused ultrasound.
المؤلفون: Morse SV; Department of Bioengineering, Imperial College London, South Kensington, London, SW7 2BP, UK., Boltersdorf T; Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City, London, W12 0BZ, UK., Harriss BI; Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City, London, W12 0BZ, UK., Chan TG; Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City, London, W12 0BZ, UK., Baxan N; Biological Imaging Centre, Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK., Jung HS; Department of Bioengineering, Imperial College London, South Kensington, London, SW7 2BP, UK., Pouliopoulos AN; Department of Bioengineering, Imperial College London, South Kensington, London, SW7 2BP, UK., Choi JJ; Department of Bioengineering, Imperial College London, South Kensington, London, SW7 2BP, UK., Long NJ; Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City, London, W12 0BZ, UK.
المصدر: Theranostics [Theranostics] 2020 Feb 03; Vol. 10 (6), pp. 2659-2674. Date of Electronic Publication: 2020 Feb 03 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-
مواضيع طبية MeSH: Brain/*diagnostic imaging , Contrast Media/*pharmacokinetics , Gadolinium/*pharmacokinetics , Rhodamines/*pharmacokinetics, Animals ; Blood-Brain Barrier ; Female ; Magnetic Resonance Imaging ; Mice ; Mice, Inbred C57BL ; Microbubbles ; Optical Imaging ; Ultrasonography
مستخلص: Gadolinium-based magnetic resonance imaging contrast agents can provide information regarding neuronal function, provided that these agents can cross the neuronal cell membrane. Such contrast agents are normally restricted to extracellular domains, however, by attaching cationic fluorescent dyes, they can be made cell-permeable and allow for both optical and magnetic resonance detection. To reach neurons, these agents also need to cross the blood-brain barrier. Focused ultrasound combined with microbubbles has been shown to enhance the permeability of this barrier, allowing molecules into the brain non-invasively, locally and transiently. The goal of this study was to investigate whether combining fluorescent rhodamine with a gadolinium complex would form a dual-modal contrast agent that could label neurons in vivo when delivered to the mouse brain with focused ultrasound and microbubbles. Methods : Gadolinium complexes were combined with a fluorescent, cationic rhodamine unit to form probes with fluorescence and relaxivity properties suitable for in vivo applications. The left hemisphere of female C57bl/6 mice (8-10 weeks old; 19.07 ± 1.56 g; n = 16) was treated with ultrasound (centre frequency: 1 MHz, peak-negative pressure: 0.35 MPa, pulse length: 10 ms, repetition frequency: 0.5 Hz) while intravenously injecting SonoVue microbubbles and either the 1 kDa Gd(rhodamine-pip-DO3A) complex or a conventionally-used lysine-fixable Texas Red® 3 kDa dextran. The opposite right hemisphere was used as a non-treated control region. Brains were then extracted and either sectioned and imaged via fluorescence or confocal microscopy or imaged using a 9.4 T magnetic resonance imaging scanner. Brain slices were stained for neurons (NeuN), microglia (Iba1) and astrocytes (GFAP) to investigate the cellular localization of the probes. Results : Rhodamine fluorescence was detected in the left hemisphere of all ultrasound treated mice, while none was detected in the right control hemisphere. Cellular uptake of Gd(rhodamine-pip-DO3A) was observed in all the treated regions with a uniform distribution (coefficient of variation = 0.4 ± 0.05). Uptake was confirmed within neurons, whereas the probe did not co-localize with microglia and astrocytes. Compared to the dextran molecule, Gd(rhodamine-pip-DO3A) distributed more homogeneously and was less concentrated around blood vessels. Furthermore, the dextran molecule was found to accumulate unselectively in microglia as well as neurons, whereas our probe was only taken up by neurons. Gd(rhodamine-pip-DO3A) was detected via magnetic resonance imaging ex vivo in similar regions to where fluorescence was detected. Conclusion : We have introduced a method to image neurons with a dual-modal imaging agent delivered non-invasively and locally to the brain using focused ultrasound and microbubbles. When delivered to the mouse brain, the agent distributed homogeneously and was only uptaken by neurons; in contrast, conventionally used dextran distributed heterogeneously and was uptaken by microglia as well as neurons. This result indicates that our probe labels neurons without microglial involvement and in addition the probe was found to be detectable via both ex vivo MRI and fluorescence. Labeling neurons with such dual-modal agents could facilitate the study of neuronal morphology and physiology using the advantages of both imaging modalities.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: MRI contrast agents; blood-brain barrier; focused ultrasound; neurons; rhodamine
المشرفين على المادة: 0 (Contrast Media)
0 (Rhodamines)
AU0V1LM3JT (Gadolinium)
تواريخ الأحداث: Date Created: 20200321 Date Completed: 20210514 Latest Revision: 20210514
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7052893
DOI: 10.7150/thno.42665
PMID: 32194827
قاعدة البيانات: MEDLINE
الوصف
تدمد:1838-7640
DOI:10.7150/thno.42665