Acoustogenic Probes: A New Frontier in Photoacoustic Imaging.

Acoustogenic Probes: A New Frontier in Photoacoustic Imaging.
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DOI:
10.1021/acs.accounts.8b00351
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发表时间:
2018-11-20
影响因子:
18.3
通讯作者:
Chan J
Chan J
中科院分区:
化学1区
文献类型:
--
作者:
Knox HJ;Chan J

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光声成像(PAI)是一种强大的成像方式,能够通过PA效应绘制生物组织对光的吸收。当发色团被光学激发时,随后以热形式的能量损失产生局部热弹性膨胀。脉冲激光的反复激发会引起压力波动,这种压力波动会在组织中传播,并以超声波的形式被检测到。通过将超声波检测与光学激发相结合,PAI可以在厘米深度进行高分辨率图像采集。PAI也相对便宜,并且依赖于近红外窗口中的安全,非电离激发光,使其成为其他常见生物医学成像方式的有吸引力的替代方案。我们小组的研究旨在开发小分子可激活探针,可用于通过PAI检测深层组织中的分析物。这些探针包含反应性触发器,在特定刺激存在下进行选择性化学反应以产生光谱变化,可以通过PAI观察到。化学调整探针和反应产物的吸光度曲线,使它们都在PA成像窗口内,当每种物质以特定波长照射时,可以实现比率成像。比率成像是这些探针的一个重要设计特征,因为它最大限度地减少了与组织相关的信号波动和仪器变化相关的误差。在这篇文章中,我们讨论了设计可用于体内研究的小分子PA探针的关键特性以及与该探针开发领域相关的挑战。我们还重点介绍了我们小组的例子,包括能够检测金属离子(Cu(II)),活性氮(NO)和氧张力(缺氧)的探针。每个目标都可以使用基于影响nir吸收染料平台的电子和光谱特性的模块化设计策略来感测。我们证明了理想的PA探针具有高摩尔吸收率,低荧光量子产率和选择性触发,可以在复杂的生物环境中可靠地报告单一分析物。探针还必须具有高度的化学和光稳定性,以便进行长期的成像研究。我们发现这些PA探针反应迅速,选择性,可用于各种疾病的小鼠模型的深层组织成像。总的来说,这些例子代表了一类新的生物医学成像工具,它们寻求使高分辨率分子成像能够改进诊断方法并阐明新的生物学发现。我们预计,小分子PA探针与新的PAI技术的结合将使与疾病进展和组织微环境定位相关的分析物的非侵入性检测成为可能。
Photoacoustic imaging (PAI) is a powerful imaging modality capable of mapping the absorption of light in biological tissue via the PA effect. When chromophores are optically excited, subsequent energy loss in the form of heat generates local thermoelastic expansion. Repeated excitation from a pulsed laser induces pressure fluctuations that propagate through tissue and can be detected as ultrasound waves. By combining ultrasonic detection with optical excitation, PAI enables high-resolution image acquisition at centimeter depths. PAI is also relatively inexpensive and relies on safe, non-ionizing excitation light in the near-infrared window, making it an attractive alternative to other common biomedical imaging modalities. Research in our group is aimed at developing small-molecule activatable probes that can be used for analyte detection in deep tissue via PAI. These probes contain reactive triggers that undergo a selective chemical reaction in the presence of specific stimuli to produce a spectral change, that can be observed via PAI. Chemically tuning the absorbance profile of the probe and the reacted product such that they are both within the PA imaging window enables ratiometric imaging when each species is irradiated at a specific wavelength. Ratiometric imaging is an important design feature of these probes as it minimizes error associated with tissue-dependent signal fluctuations and instrumental variation. In this account, we discuss key properties for designing small-molecule PA probes that can be applied for in vivo studies and the challenges associated with this area of probe development. We also highlight examples from our group including probes capable of detecting metal ions (Cu(II)), reactive nitrogen species (NO), and oxygen tension (hypoxia). Each of these targets can be sensed using a modular design strategy based on influencing the electronic and spectral properties of a NIR-absorbing dye platform. We demonstrate that ideal PA probes have high molar absorptivity, low fluorescence quantum yields, and selective triggers that can reliably report on a single analyte in a complex biological setting. Probes must also be highly chemo- and photostable to enable long term imaging studies. We show that these PA probes react rapidly and selectively and can be utilized for deep-tissue imaging in mouse models of various diseases. Overall, these examples represent a new class of biomedical imaging tools that seek to enable high resolution molecular imaging capable of improving diagnostic methods and elucidating new biological discoveries. We anticipate that the combination of small-molecule PA probes with new PAI technology will enable non-invasive detection of analytes relevant to disease progression and mapping of tissue microenvironments.
DOI: 10.1021/bi2000966
发表时间: 2011-04-05
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影响因子: 2.9
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期刊: ADVANCED CONCEPTS IN FLUORESCENCE SPECTROSCOPY, PT A: SMALL MOLECULE SENSING
影响因子: --
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DOI: 10.1021/acschembio.8b00099
发表时间: 2018-07-01
影响因子: 4
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DOI: 10.1021/acs.biochem.7b00888
发表时间: 2018-01-16
期刊: Biochemistry
影响因子: 2.9
作者:
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