Localization of Fluorescent Targets in Deep Tissue With Expanded Beam Illumination for Studies of Cancer and the Brain

Localization of Fluorescent Targets in Deep Tissue With Expanded Beam Illumination for Studies of Cancer and the Brain
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DOI:
10.1109/tmi.2020.2972200
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发表时间:
2020-07-01
影响因子:
10.6
通讯作者:
Webb, Kevin J.
Webb, Kevin J.
中科院分区:
工程技术1区
文献类型:
--
作者:
Bentz, Brian Z.;Mahalingam, Sakkarapalayam M.;Webb, Kevin J.

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通过毫米或厘米的组织成像荧光在体内有重要的应用,如指导手术和研究大脑。通常,重要的信息是多个光学报告器之一的位置,而不是局部几何形状的细节,这促使需要提供此信息的定位方法。我们提出了一种基于扩散模型的优化方法,用于扩展光束照明下深层组织中荧光不均匀性的快速定位,简化了实验和重建。我们表明,可以在假设组织参数均匀的情况下估计荧光不均匀性的位置,而无需对激发剖面进行建模,从而减少了计算负担并提高了方法的实用性。我们做了两个实验作为论证。首先,使用近红外叶酸靶向荧光剂(OTL38)定位小鼠肿瘤。该结果表明,定位可以快速提供肿瘤深度信息,从而减少荧光引导手术对健康组织的损伤。其次,将另一种近红外荧光剂(ATTO647N)注射到大鼠的大脑中,并通过完整的颅骨和表面组织定位。这一结果将使蛋白质聚集和神经元信号的研究成为可能。
Imaging fluorescence through millimeters or centimeters of tissue has important in vivo applications, such as guiding surgery and studying the brain. Often, the important information is the location of one of more optical reporters, rather than the specifics of the local geometry, motivating the need for a localization method that provides this information. We present an optimization approach based on a diffusion model for the fast localization of fluorescent inhomogeneities in deep tissue with expanded beam illumination that simplifies the experiment and the reconstruction. We show that the position of a fluorescent inhomogeneity can be estimated while assuming homogeneous tissue parameters and without having to model the excitation profile, reducing the computational burden and improving the utility of the method. We perform two experiments as a demonstration. First, a tumor in a mouse is localized using a near infrared folate-targeted fluorescent agent (OTL38). This result shows that localization can quickly provide tumor depth information, which could reduce damage to healthy tissue during fluorescence-guided surgery. Second, another near infrared fluorescent agent (ATTO647N) is injected into the brain of a rat, and localized through the intact skull and surface tissue. This result will enable studies of protein aggregation and neuron signaling.