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利用传统荧光显微镜和深度学习可视化局部药物摄取情况。

Visualizing topical drug uptake with conventional fluorescence microscopy and deep learning.

作者信息

Evans Conor L, Hermsmeier Maiko, Yamamoto Akira, Chan Kin F

机构信息

Massachusetts General Hospital, Wellman Center for Photomedicine, Boston 02114, USA.

BioPharmX, Inc., 115 Nicholson Ln, San Jose, CA 95134, USA.

出版信息

Biomed Opt Express. 2020 Nov 4;11(12):6864-6880. doi: 10.1364/BOE.405502. eCollection 2020 Dec 1.

DOI:10.1364/BOE.405502
PMID:33408967
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7747892/
Abstract

Mapping the uptake of topical drugs and quantifying dermal pharmacokinetics (PK) presents numerous challenges. Though high resolution and high precision methods such as mass spectrometry offer the means to quantify drug concentration in tissue, these tools are complex and often expensive, limiting their use in routine experiments. For the many topical drugs that are naturally fluorescent, tracking fluorescence emission can be a means to gather critical PK parameters. However, skin autofluorescence can often overwhelm drug fluorescence signatures. Here we demonstrate the combination of standard epi-fluorescence imaging with deep learning for the visualization and quantification of fluorescent drugs in human skin. By training a U-Net convolutional neural network on a dataset of annotated images, drug uptake from both high "infinite" dose and daily clinical dose regimens can be measured and quantified. This approach has the potential to simplify routine topical product development in the laboratory.

摘要

绘制局部用药的摄取情况并量化皮肤药代动力学(PK)存在诸多挑战。尽管诸如质谱等高分辨率和高精度方法提供了量化组织中药物浓度的手段,但这些工具复杂且往往成本高昂,限制了它们在常规实验中的应用。对于许多具有天然荧光的局部用药而言,追踪荧光发射可以作为获取关键药代动力学参数的一种方法。然而,皮肤自身荧光常常会掩盖药物的荧光信号。在此,我们展示了将标准落射荧光成像与深度学习相结合,用于可视化和量化人体皮肤中的荧光药物。通过在注释图像数据集上训练U-Net卷积神经网络,可以测量和量化高“无限”剂量和日常临床剂量方案下的药物摄取情况。这种方法有可能简化实验室中的常规局部用药产品开发。

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本文引用的文献

1
Label-Free Quantification of Pharmacokinetics in Skin with Stimulated Raman Scattering Microscopy and Deep Learning.无标记定量皮肤药代动力学的拉曼散射显微镜和深度学习研究
J Invest Dermatol. 2021 Feb;141(2):395-403. doi: 10.1016/j.jid.2020.06.027. Epub 2020 Jul 22.
2
Imaging and quantifying drug delivery in skin - Part 2: Fluorescence andvibrational spectroscopic imaging methods.在皮肤中成像和定量药物输送 - 第 2 部分:荧光和振动光谱成像方法。
Adv Drug Deliv Rev. 2020 Jan 1;153:147-168. doi: 10.1016/j.addr.2020.03.003. Epub 2020 Mar 23.
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Time-resolved fluorescence microscopy with phasor analysis for visualizing multicomponent topical drug distribution within human skin.相衬分析的时间分辨荧光显微镜用于可视化人皮肤内多组分局部药物分布。
Sci Rep. 2020 Mar 24;10(1):5360. doi: 10.1038/s41598-020-62406-z.
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Imaging and quantifying drug delivery in skin - Part 1: Autoradiography and mass spectrometry imaging.医学成像和定量皮肤药物递送 - 第 1 部分:放射自显影和质谱成像。
Adv Drug Deliv Rev. 2020 Jan 1;153:137-146. doi: 10.1016/j.addr.2019.11.004. Epub 2019 Nov 26.
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Characterization of human cutaneous tissue autofluorescence: implications in topical drug delivery studies with fluorescence microscopy.人体皮肤组织自发荧光的表征:在荧光显微镜下局部药物递送研究中的意义。
Biomed Opt Express. 2018 Oct 12;9(11):5400-5418. doi: 10.1364/BOE.9.005400. eCollection 2018 Nov 1.
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Visualization of drug distribution of a topical minocycline gel in human facial skin.局部用米诺环素凝胶在人面部皮肤中药物分布的可视化。
Biomed Opt Express. 2018 Jun 27;9(7):3434-3448. doi: 10.1364/BOE.9.003434. eCollection 2018 Jul 1.
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Current Applications and Future Impact of Machine Learning in Radiology.机器学习在放射学中的当前应用和未来影响。
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Non-Euclidean phasor analysis for quantification of oxidative stress in ex vivo human skin exposed to sun filters using fluorescence lifetime imaging microscopy.非欧几里得相量分析用于荧光寿命成像显微镜定量检测体外人体皮肤暴露于防晒剂时的氧化应激。
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On tuning the fluorescence emission of porphyrin free bases bonded to the pore walls of organo-modified silica.关于调节与有机改性二氧化硅孔壁结合的卟啉游离碱的荧光发射。
Molecules. 2014 Feb 21;19(2):2261-85. doi: 10.3390/molecules19022261.
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