CAREER: Image critical dental diseases that current dental X-ray/CT fails to detect, without ionizing radiation

超过三分之二的美国人必须定期接受牙科成像。目前的牙科诊断主要依靠牙科X光/CT(Computer Tomography，计算机断层摄影)，存在以下几个主要缺陷：1)目前的牙科X光/CT不能发现一些发病率较高的危重疾病：例如，34-74%的人有牙裂。由于高度多变的症状，裂缝是出了名的难以诊断，即使是有经验的牙医。2)牙科X射线的电离辐射可增加脑膜瘤、甲状腺癌和低出生体重儿的出生风险。电离辐射在儿童中更受关注，因为他们需要接受比正常患者高3-6倍的牙科X光/CT检查，而在牙科专业人员中，他们操作X光/CT的频率要比正常患者高得多。3)将笨重的X射线/CT传感器固定在许多人(如儿童)手中也是一项挑战。本项目旨在通过开发一种新的牙科成像方案来解决这些缺点，该方案使用实验室设计的灵敏的近红外荧光光子成像系统，由高分辨率相机和光谱设备组成，用于实时牙科成像。此外，该项目将教授学生和公众有关尖端生物成像知识的知识，以帮助他们应对实际挑战，如COVID-19。项目目标是开发一种灵敏的近红外荧光成像系统，包括高分辨率相机和光谱设备，以及纳米荧光团，以实时成像关键的牙齿结构和疾病，包括那些最先进的牙科X射线/CT无法检测到的疾病，并消除电离辐射的风险和固定咬伤笨重传感器的必要性。为了实现这一目标，将采用以下方法：1)设计高分辨率的牙科成像系统，研究染料在牙齿组织中分布的基本机制以及染料分布对成像性能的影响；2)将该牙科成像方案与其他先进的牙科成像方案进行系统的比较，以研究动物和人类牙齿上的关键牙病和结构；3)通过含漱水将吲哚青绿递送到牙齿上，优化牙科成像策略。本项目的研究活动具有以下几个方面的智力意义：a)本研究促进了跨学科知识的发展。首先，这项研究可能会促进对染料在软、硬生物材料中生物分布的基本理解。FDA批准的近红外染料吲哚青绿是众所周知的通过血液和淋巴循环分布到软组织中的染料。然而，吲哚青绿如何分布到坚硬的结构中，如牙齿，仍然是未知的。这项研究将探讨吲哚青绿在硬结构中的分布方式，成像因素(如染料用量、观察时间)如何影响生物分布，以及这些因素如何定量地影响成像性能。其次，这项研究促进了人们对软硬生物结构如何与不同的电磁波(如近红外I波(700-1000 nm)、近红外II波(1000-1700 nm)和X射线)相互作用以及这些相互作用如何影响成像各种牙科疾病时电磁波和成像参数的选择的基本理解。B)这项工作在牙科成像领域具有创新性。这项工作使用FDA批准的吲哚青绿作为生物兼容的近红外II荧光团，以促进人类应用程序的翻译，以及与传统静脉注射相反的用户友好的染料口水输送；这两项工作都是该领域的开创性工作。C)这项工作具有变革性。与目前的牙科X射线/CT(10-2-101 nm)成像相比，这项工作使用完全不同的光(700-1700 nm)来消除电离辐射，从而通过提供不同角度/距离的连续实时牙科成像而导致牙科实践的革命性变化，而不会影响健康。该项目由工程局的电气、通信和网络系统(ECCS)和已建立的刺激竞争研究计划(EPSCoR)联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

More than 2/3 of Americans have to receive dental imaging routinely. Current dental diagnosis largely relies on dental X-ray/CT (computed tomography), with several major drawbacks: 1) current dental X-ray/CT fails to detect some critical diseases with high incidence rates: for instance, 34-74% of people have tooth cracks. Due to highly variable symptoms, crack is notoriously difficult to be diagnosed even for experienced dentists. 2) the ionizing radiation of dental X-ray was found to increase the risk of meningioma, thyroid cancer, and delivery of low-birth-weight baby. Ionizing radiation is more concerned in children, as they are required to take 3-6 times more frequent dental X-ray/CT, and in dental professionals, as they operate X-ray/CT much more frequently, than normal patients. 3) It is also challenging to hold bulky X-ray/CT sensor immobile by many people, such as children. This project is to address these drawbacks by developing a novel dental imaging scheme with a lab-designed sensitive near-infrared fluorescence photonic imaging system, consisting of a high-resolution camera and a spectroscopic device, for real-time dental imaging. In addition, this project will teach students and educate the general public on the cutting-edge bio-imaging knowledge to help them tackle practical challenges, such as COVID-19.The project goal is to develop a sensitive near-infrared fluorescence imaging system, including a high-resolution camera and a spectroscopic device, together with nanofluorophore, to image critical dental structures and diseases, including those undetectable by state-of-the-art dental X-ray/CT, in real time, and to eliminate the risks of ionizing radiation and the necessity of biting bulky sensors immobile. To achieve the goal, the following approaches are to be used: 1) Design a high-resolution dental imaging system and study the fundamental mechanism of dye distribution in dental tissues and the impact of dye distribution on imaging performance; 2) Systematically compare this dental imaging scheme to other state-of-the-art imaging modalities on critical dental diseases and structures on both animal and human teeth; 3) Optimize the dental imaging strategy with indocyanine green delivery by mouthwash. The research activity of this project has intellectual significances in several aspects: A) This research advances interdisciplinary knowledge. First, this research may advance the fundamental understanding of bio-distributions of dye in soft and hard biomaterials. FDA-approved near-infrared dye, the indocyanine green, is well understood for the distribution into soft tissues via blood and lymphatic circulations. However, how indocyanine green is distributed into hard structures, such as teeth, remains unknown. This study will investigate the indocyanine green distribution approaches in hard structures, how the biodistribution is affected by imaging factors (for example, dye dosage, observation time) and how these factors may quantitatively impact the imaging performance. Second, this research advances the fundamental understanding of how hard and soft biostructures interacts with different electromagnetic waves (such as near-infrared I (700-1000 nm), near-infrared II (1000-1700 nm), and X-ray) and how these interactions impact the choice of electromagnetic waves and imaging parameters when imaging various dental diseases. B) This work is innovative in the field of dental imaging. This work employs FDA-approved indocyanine green as a biocompatible near-infrared II fluorophore to facilitate the translation of human applications, and a user-friendly “mouthwash” delivery of dye, as opposed to the traditional intravenous injection; both are the pioneering works in the field. C) This work is transformative. In contrast with the current dental X-ray/CT (10-2-101 nm) imaging, this works uses completely different light (700-1700 nm) to eliminate the ionizing radiation, thus leading to the revolutionary change of dental practice by providing continuous real-time dental imaging at various angles/distances without health concerns.This project is being jointly funded by Electrical, Communications and Cyber Systems (ECCS) in Engineering Directorate and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.