Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.
Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.
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DOI：
10.1117/1.jbo.29.1.016004
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发表时间：
2024-01
影响因子：
3.5
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中科院分区：
文献类型：
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外科医生在临床上使用荧光引导来可视化手术区域中难以或不可能通过肉眼检测到的解剖学和/或生理学现象。这种现象包括组织灌注或关于被切除的疾病的分子表型信息。传统的荧光引导手术依赖于长的微秒级激光脉冲来激发荧光探针。然而，该技术仅提供二维信息;不提供关键的深度信息，例如组织表面以下的恶性肿瘤的位置。我们开发了一种深度传感成像技术，利用光探测和测距（LiDAR）飞行时间（TOF）技术来感测目标组织的深度，同时克服组织光学特性和荧光探针浓度的影响。该技术是基于一个大格式（），二进制，门控，单光子雪崩二极管（SPAD）传感器与18 ps的时间门阶跃，与皮秒脉冲激光同步。开发了传感器的快速响应，并通过快速时间缓解数据的分析模型拟合测试了其在组织样幻影中定量深度处的荧光夹杂物和光学性质的能力。经过数据的校准和算法提取后，SPAD LiDAR技术允许对嵌入组织样幻影中的荧光内含物进行亚毫米分辨率的深度感测，最大深度为5毫米。该方法即使在存在可变组织光学特性的情况下也提供稳健的深度感测，并且将荧光深度的影响与吸收和散射变化分开。使用SPAD相机的LiDAR TOF荧光成像提供荧光强度图像和荧光的时间分布，其可用于确定信号在宽视场上发射的深度。所提出的工具能够在组织中更高的深度处进行荧光成像，并且具有比标准的稳态荧光成像工具更高的空间精度，所述标准的稳态荧光成像工具例如基于强度的近红外荧光成像、光学相干断层扫描、拉曼光谱或共焦显微镜。将该技术集成到标准手术工具中可以实现对切除边界的快速、更准确的估计，从而提高外科医生的功效和效率，并最终改善患者的预后。
Fluorescence guidance is used clinically by surgeons to visualize anatomical and/or physiological phenomena in the surgical field that are difficult or impossible to detect by the naked eye. Such phenomena include tissue perfusion or molecular phenotypic information about the disease being resected. Conventional fluorescence-guided surgery relies on long, microsecond scale laser pulses to excite fluorescent probes. However, this technique only provides two-dimensional information; crucial depth information, such as the location of malignancy below the tissue surface, is not provided. We developed a depth sensing imaging technique using light detection and ranging (LiDAR) time-of-flight (TOF) technology to sense the depth of target tissue while overcoming the influence of tissue optical properties and fluorescent probe concentration. The technology is based on a large-format (), binary, gated, single-photon avalanche diode (SPAD) sensor with an 18 ps time-gate step, synchronized with a picosecond pulsed laser. The fast response of the sensor was developed and tested for its ability to quantify fluorescent inclusions at depth and optical properties in tissue-like phantoms through analytical model fitting of the fast temporal remission data. After calibration and algorithmic extraction of the data, the SPAD LiDAR technique allowed for sub-mm resolution depth sensing of fluorescent inclusions embedded in tissue-like phantoms, up to a maximum of 5 mm in depth. The approach provides robust depth sensing even in the presence of variable tissue optical properties and separates the effects of fluorescence depth from absorption and scattering variations. LiDAR TOF fluorescence imaging using an SPAD camera provides both fluorescence intensity images and the temporal profile of fluorescence, which can be used to determine the depth at which the signal is emitted over a wide field of view. The proposed tool enables fluorescence imaging at a higher depth in tissue and with higher spatial precision than standard, steady-state fluorescence imaging tools, such as intensity-based near-infrared fluorescence imaging, optical coherence tomography, Raman spectroscopy, or confocal microscopy. Integration of this technique into a standard surgical tool could enable rapid, more accurate estimation of resection boundaries, thereby improving the surgeon’s efficacy and efficiency, and ultimately improving patient outcomes.