Temperature Modulated-Fluorescence Tomography: A New Modality for Cancer Imaging

温度调制荧光断层扫描：癌症成像的新模式

• 批准号: 8546153
• 负责人: Tiffany Kwong
• 金额: $ 3.53万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-14 至 2015-09-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546153
• 关键词: Academia; Adult; Algorithms; American; Anatomy; Animal Model; Animals; Biochemical; Biological; Cancer Biology; Cancer Etiology; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Clinical Research; Color; Contrast Media; Detection; Development; Diffuse; Disease; Encapsulated; Evaluation; Experimental Designs; Feasibility Studies; Fluorescence; Focused Ultrasound Therapy; Glutamate Carboxypeptidase II; Goals; Gold; Grant; Guidelines; Hot Spot; Image; Imaging technology; Indocyanine Green; Industry; Injection of therapeutic agent; Institutes; Lasers; Letters; Light; Magnetic Resonance Imaging; Malignant neoplasm of prostate; Medicine; Micelles; Modality; Molecular; Molecular Probes; Molecular Target; Mus; Nature; Noise; Nonionizing Radiation; Nuclear; Nude Mice; Optics; Organ; Outcome; Pathway interactions; Penetration; Performance; Play; Pluronics; Process; Property; Prostatic Neoplasms; Publishing; Radiation; Research; Research Personnel; Resolution; Role; Scanning; Second Primary Cancers; Signal Transduction; Spottings; Surface; System; Systems Development; Techniques; Temperature; Testing; Thick; Tissues; Training; Translations; Tube; Ultrasonic Transducer; Ultrasonic wave; Ultrasonography; Validation; Variant; base; cancer imaging; cancer type; clinical practice; cost; cost effective; fluorescence imaging; image reconstruction; imaging modality; imaging probe; improved; in vivo; innovation; instrumentation; light intensity; men; molecular imaging; nanocapsule; novel; novel strategies; optical imaging; performance tests; preclinical study; prostate cancer model; prototype; quantum; reconstruction; simulation; tomography; tumor

DESCRIPTION (provided by applicant): According to the CDC, among US men, cancer of the prostate is the most common type of cancer and the second leading cause of cancer death. Due to the diffuse nature of prostate cancer, there is a need for safe, inexpensive, and portable prostate tumor imaging, which MRI or nuclear imaging cannot satisfy. As one of the most sensitive in vivo molecular imaging modalities, fluorescence imaging has great potential to play an important role in preclinical and clinical studies. Indeed, in vivo fluorescence optical imaging extends across a wide range of applications, from cellular to organ levels. Unfortunately, in organ level applications, fluorescence imaging suffers from low resolution due to the high scattering nature of the biological tissue especially in deep tissue. Extensive effort has been spent to improve the resolution of fluorescence tomography (FT) by research groups from academia and industry in the last decade. However, approaches such as integrating FT with other anatomic imaging modalities such as MRI or CT does not perform well if the fluorescent target cannot be localized in the anatomical image. There are several techniques that attempt to modulate fluorescence signals using ultrasound to achieve higher resolution. However, low modulation efficiency and extremely low signal to noise ratio (SNR) are the two primary factors that make the implementation of these techniques difficult. Therefore, the low quantitative accuracy and resolution of fluorescence imaging remain as the main barriers for clinical translation of this powerful technique. To overcome these limitations, our main goal in this proposal is to develop an entirely new approach "Temperature-modulated fluorescence tomography (TM-FT)" that can provide high resolution images at depths up to 6 cm without sacrificing the exceptional sensitivity of fluorescence-based detection. There are two key components to this highly innovative approach: a) Temperature sensitive florescent molecular probes (thermo-dots) and b) High Intensity Focused Ultrasound (HIFU) based modulation of tissue temperature (only 3-50C) with high spatial resolution. The small size of the focal spot (~1mm) allows imaging the distribution of these temperature sensitive agents with not only high spatial resolution but also high quantitative accuracy. Development of this novel system will include: development and optimization of the TM-FT reconstruction algorithm, development of the TM-FT system and evaluation with phantom studies, and finally, validation with in vivo studies. This training proposal is geared toward the first in vivo feasibility studies of this nove imaging modality. The outcome of this proposal could be a radiation free, cost-effective, and portable tumor imaging system. Mice bearing orthotopic prostate cancer model will be used to test the hypothesis that "TM-FT will provide quantitatively more accurate and higher resolution fluorescence images compared to a stand-alone FT system". If successful, the outcome will be the beginning of a new imaging modality.

描述（由申请人提供）：根据疾病预防控制中心的数据，在美国男性中，前列腺癌是最常见的癌症类型，也是癌症死亡的第二大原因。由于前列腺癌的弥漫性，需要安全、廉价且便携式的前列腺肿瘤成像，而 MRI 或核成像无法满足这一需求。作为最灵敏的体内分子成像方式之一，荧光成像具有在临床前和临床研究中发挥重要作用的巨大潜力。事实上，体内荧光光学成像 涵盖从细胞水平到器官水平的广泛应用。不幸的是，在器官水平应用中，由于生物组织（尤其是深层组织）的高散射特性，荧光成像分辨率较低。过去十年来，学术界和工业界的研究小组为提高荧光断层扫描（FT）的分辨率付出了巨大的努力。然而，如果荧光目标无法在解剖图像中定位，那么将 FT 与其他解剖成像模式（例如 MRI 或 CT）集成等方法的效果就不佳。有几种技术尝试使用超声波调制荧光信号以实现更高分辨率。然而，低调制效率和极低的信噪比（SNR）是导致这些技术实施困难的两个主要因素。因此，荧光成像的低定量精度和分辨率仍然是这种强大技术临床转化的主要障碍。为了克服这些限制，我们在本提案中的主要目标是开发一种全新的方法“温度调制荧光断层扫描（TM-FT）”，它可以在深度达 6 厘米的情况下提供高分辨率图像，而不会牺牲基于荧光的检测的卓越灵敏度。这种高度创新的方法有两个关键组成部分：a) 温度敏感荧光分子探针（热点）和 b) 基于高强度聚焦超声 (HIFU) 的组织温度调节（仅 3-50C），具有高空间分辨率。焦斑的小尺寸（~1mm）允许对这些温度敏感剂的分布进行成像，不仅具有高空间分辨率，而且具有高定量精度。该新颖系统的开发将包括：TM-FT 重建算法的开发和优化、TM-FT 系统的开发和模型研究的评估，最后是体内研究的验证。该培训计划旨在针对这种新颖的成像方式进行首次体内可行性研究。该提案的成果可能是一种无辐射、经济高效的便携式肿瘤成像系统。携带原位前列腺癌模型的小鼠将用于检验“与独立 FT 系统相比，TM-FT 将提供定量更准确、分辨率更高的荧光图像”的假设。如果成功，结果将是新成像模式的开始。