Label-free imaging of biological chromophores using photothermal signatures

在过去的三十年中，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获得了极大的关注。在这些技术中，对比度的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是提高分子灵敏度的无标记解决方案。拟议的研究计划打算将这一想法纳入引入新技术，并提高当前最先进的光学分子对比成像技术。****在研究主题1中，我们将开发一种改进的光热光学相干层析成像（PT-OCT）系统，用于利用其光热特征来可视化和研究发色团。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，将雷达匹配滤波检测方法引入到PT-OCT领域。在这里，光热光束将以编码方式进行强度调制，并通过相互关联匹配滤波研究相应的OCT相位信号。这种方法有望通过允许重叠发色团/吸收剂的个体响应的反卷积来提高PT-OCT分辨率。该研究主题的结果不仅对加拿大公众有用，作为疾病诊断成像设备，而且对加拿大研究人员有用，作为表征分子物种和研究其活动的无标签成像工具。所开发的知识和技术有潜力用于早期疾病诊断、血氧和血糖水平的量化以及药物发现。****在研究主题2中，我们将以PI之前的研究为出发点，开发一种热光子长波红外（LWIR）龋齿检测系统。从热波科学的角度来看，在牙齿样品中使用LWIR检测波段是新颖的，也是有益的。该系统将结合单频和编码强度调制（即锁定和匹配滤波器检测），以显示早期牙齿脱矿。本课题的研究成果对加拿大公众作为早期龋病检测技术是有用的。预计加拿大政府也将从这种早期检测技术中受益，因为从长远来看，它可以降低牙科保健的费用。LWIR热光子系统的另一个潜在应用是对制造缺陷和材料缺陷的无损评估。****五名研究生和五名本科生将在五年内接受培训，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.**