Label-free imaging of biological chromophores using photothermal signatures

基于光学的成像技术由于其安全的非电离性质和高分辨率而在过去三十年中获得了极大的关注。这些技术中的对比度来源主要是来自组织不均匀性的光散射。然而，光散射对早期疾病引起的异常不敏感，因为这些变化通常在分子水平上开始。从光吸收获得诊断对比度是用于提高分子灵敏度的无标记解决方案。拟议的研究计划旨在将这一想法引入新技术，并提高目前基于光学的分子对比成像的最新水平。 在研究主题1中，我们将开发一种改进的光热光学相干断层扫描（PT-OCT）系统，用于可视化和研究发色团使用它们的光热签名。光热响应的振幅和相位谱将用于研究发色团/吸收剂的物理性质。此外，雷达匹配滤波检测方法将被引入到PT-OCT领域。在这里，光热光束将被调制的强度编码的方式和相应的OCT相位信号将被研究与互相关匹配滤波。这种方法预期通过允许来自重叠发色团/吸收剂的个体响应的去卷积来提高PT-OCT分辨率。这一研究主题的成果不仅对加拿大公众作为疾病诊断成像设备有用，而且对加拿大研究人员作为表征分子物种和研究其活动的无标记成像工具也有用。所开发的知识和技术有可能用于早期疾病诊断、血氧和葡萄糖水平的量化以及药物发现。 在研究主题二中，以PI先前的研究为出发点，我们将开发一种热光子长波红外（LWIR）龋齿检测系统。在牙齿样本中使用长波红外检测波段是新颖的，并且从热波科学的观点来看也是有益的。单频和编码强度调制（即锁定和匹配滤波器检测）将被纳入系统，以揭示早期牙齿脱矿。本研究主题的结果是有用的加拿大公众作为早期龋齿检测技术。从长远来看，加拿大政府也有望从这种早期检测技术中受益，降低牙科护理的成本。长波红外热光子系统的另一个潜在应用是对材料中的制造缺陷和缺陷进行非破坏性评估。 5名研究生和5名本科生将在5年内接受培训，获得未来就业所需的一系列技术和软技能。

Optics-based imaging technologies have gained significant attention during the past three decades due to their safe non-ionizing nature and high resolving power. The source of contrast in these technologies is predominantly light scattering from tissue inhomogeneity. However, light scattering is insensitive to early disease-induced abnormalities as these changes typically initiate at the molecular level. Obtaining diagnostic contrast from light absorption is a label-free solution for improving the molecular sensitivity. The proposed research program intends to incorporate this idea to introduce new technologies as well as to enhance the current state-of-the-art in optics-based molecular-contrast imaging.  In research theme 1, we will develop a modified photo-thermal optical coherence tomography (PT-OCT) system for visualizing and studying chromophores using their photo-thermal signatures. The amplitude and phase spectrums of photo-thermal responses will be used to study the physical properties of chromophores/absorbers. Moreover, radar matched-filter detection method will be introduced to the PT-OCT field. Here the photo-thermal beam will be intensity modulated in a codded manner and the corresponding OCT phase signal will be studied with cross-correlation matched-filtering. This approach is expected to improve PT-OCT resolution by allowing for deconvolution of individual responses from overlapping chromophores/absorbers. The outcomes of this research theme are useful not only to Canadian public as a disease diagnostic imaging device, but also to Canadian researchers as a label-free imaging tool for characterizing molecular species and studying their activities. The developed knowledge and techniques have the potential to be used in early disease diagnosis, quantification of blood oxygenation and glucose levels, and drug discovery.  In research theme 2, taking PI's previous research as a starting point, we will develop a thermo-photonic long-wavelength infrared (LWIR) dental caries detection system. Use of LWIR detection band in dental samples is novel and also beneficial from the thermal-wave science point of view. Single-frequency and codded intensity modulation (i.e. lock-in and matched-filter detection) will be incorporated in the system to reveal early tooth demineralization. The outcomes of this research theme are useful to Canadian public as an early dental caries detection technology. The Government of Canada is also expected to benefit from this early detection technology by lowering the cost of dental care in the long run. Another potential application of the LWIR thermo-photonic system is non-destructive evaluation of manufacturing flaws and defects in materials.  Five graduate students and five undergraduate students will be trained within 5 years, gaining a spectrum of technical and soft skills required for their future employment.