Optoacoustic imaging offers the promise of high spatial resolution and, at the same time, penetration depths well beyond the conventional optical imaging technologies, advantages that would be favorable for a variety of clinical applications. However, similar to optical fluorescence imaging, exogenous contrast agents, known as sonophores, need to be developed for molecularly targeted optoacoustic imaging. Despite numerous optoacoustic contrast agents that have been reported, there is a need for more rational design of sonophores. Here, using a library screening approach, we systematically identified and evaluated twelve commercially available near-infrared (690–900 nm) and highly absorbing dyes for multi-spectral optoacoustic tomography (MSOT). In order to achieve more accurate spectral deconvolution and precise data quantification, we sought five practical mathematical methods, namely direct classical least squares based on UV-Vis (UV/Vis-DCLS) or optoacoustic (OA-DCLS) spectra, non-negative LS (NN-LS), independent component analysis (ICA) and principal component analysis (PCA). We found that OA-DCLS is the most suitable method, allowing easy implementation and sufficient accuracy for routine analysis. Here, we demonstrate for the first time that our biocompatible nanoemulsions (NEs), in combination with near-infrared and highly absorbing dyes, enable non-invasive in vivo MSOT detection of tumors. Specifically, we found that NE-IRDye QC1 offers excellent optoacoustic performance and detection compared to related near-infrared NEs. We demonstrate that when loaded with low fluorescent or dark quencher dyes, NEs represent a flexible and new class of exogenous sonophores suitable for non-invasive pre-clinical optoacoustic imaging.

中文翻译：

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超声增强纳米乳剂用于癌症的光声成像†

光声成像提供了高空间分辨率的希望，同时，其穿透深度远远超过了常规的光学成像技术，这些优势将有利于各种临床应用。然而，类似于光学荧光成像，需要开发被称为声泳的外源性造影剂，以进行分子靶向的光声成像。尽管已经报道了许多光声造影剂，但是仍需要更合理地设计声泳信号。在这里，我们使用库筛选方法，系统地鉴定和评估了十二种可商购的近红外（690-900 nm）和高吸收染料，用于多光谱光声层析成像（MSOT）。为了实现更准确的光谱去卷积和精确的数据量化，我们寻求了五种实用的数学方法，即基于UV-Vis（UV / Vis-DCLS）或光声（OA-DCLS）光谱的直接经典最小二乘法，非负LS（NN-LS），独立成分分析（ICA）和主成分分析（PCA）。我们发现OA-DCLS是最合适的方法，可以轻松实现，并且对于常规分析具有足够的准确性。在这里，我们首次证明了我们的生物相容性纳米乳剂（NEs）与近红外和高吸收性染料相结合，能够实现非侵入性 易于实施，并且对于常规分析具有足够的准确性。在这里，我们首次证明了我们的生物相容性纳米乳剂（NEs）与近红外和高吸收性染料相结合，能够实现非侵入性 易于实施，并且对于常规分析具有足够的准确性。在这里，我们首次证明了我们的生物相容性纳米乳剂（NEs）与近红外和高吸收性染料相结合，能够实现非侵入性体内MSOT检测肿瘤。具体来说，我们发现NE-IRDye QC1与相关的近红外NE相比具有出色的光声性能和检测能力。我们证明，当负载低荧光或深色猝灭染料时，NE代表了适用于非侵入性临床前光声成像的灵活和新型的外源声泳。