Background-free molecular imaging using modulated photoacoustics and targeted contrast agent

使用调制光声和靶向造影剂进行无背景分子成像

• 批准号: 10385745
• 负责人: ROBERT M DICKSON
• 金额: $ 64.24万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385745
• 关键词: Abbreviations; Algorithms; Antibodies; Area; Binding; Biopsy; Blood; Breast Cancer Model; Breast Melanoma; Caliber; Cancer Patient; Cardiology; Cells; Clinical; Color; Contrast Media; Coupled; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Disseminated Malignant Neoplasm; Dyes; Early Diagnosis; Ensure; Exhibits; Fluorescence; Formulation; Frequencies; Generations; Glossary; Goals; Histologic; Histology; Hour; Image; Imaging Device; Imaging Techniques; Imaging technology; Lasers; Lipids; Malignant Neoplasms; Measurement; Medical Imaging; Metastatic Neoplasm to Lymph Nodes; Metastatic breast cancer; Micrometastasis; Molecular; Molecular Target; Mus; Neoplasm Metastasis; Noise; Oncology; Operative Surgical Procedures; Optics; Outcome; Outcome Study; Pathology; Patient-Focused Outcomes; Physiologic pulse; Process; Pump; Research; Resolution; Rest; Rose Bengal; Sensitivity and Specificity; Sentinel Lymph Node; Signal Transduction; Silicon Dioxide; Source; Surface; System; Technology; Therapeutic; Time; Tissue imaging; Tissues; Ultrasonic Transducer; Ultrasonography; Whole Blood; absorption; base; biomaterial compatibility; cancer cell; cancer therapy; chromophore; clinical imaging; clinically relevant; contrast imaging; cost effective; cyanine dye 5; design; detection sensitivity; draining lymph node; image processing; imaging approach; imaging platform; imaging system; improved; in vivo; instrumentation; irradiation; lymph nodes; malignant breast neoplasm; molecular imaging; mouse model; nanocluster; nanoparticle; optical imaging; outcome prediction; particle; photoacoustic imaging; portability; programs; prototype; receptor; research clinical testing; response; targeted imaging; ultrasound

ABSTRACT The goal of this research program is to develop an advanced, noninvasive, molecularly specific imaging tech- nology – ultrasound-guided modulated photoacoustic imaging augmented by optically-activatable, targeted con- trast agents, capable of immediate, accurate, background-free assessment of pathologies in vivo. The underlying hypothesis of this project is that ultrasound-guided photoacoustic imaging of optically modulated contrast agents can be performed in real time, yielding immediate diagnostic information. The approach is based on the unique combination of an optically-activatable molecularly-targeted imaging contrast agent and corresponding laser/ul- trasound imaging device. Specifically, development of a highly-sensitive imaging contrast agent consisting of silica nanoparticles doped with optically-activatable photoabsorbers and coated by an antibody-functionalized lipid shell will be undertaken. The photoabsorbers embedded in the silica core exhibit ~50s-lived, transient near-infrared optical absorption upon prior red laser irradiation. The contrast agent will be imaged using a clinical ultrasound (US) imaging system, interfaced with two (pump/probe) pulsed laser sources, operating in either ultrasound or photoacoustic imaging modes. Pump laser pulses will repeatedly activate the contrast agent, thus allowing for probe laser pulses to generate photoacoustic signal that can be processed to generate background- free modulated photoacoustic (mPA) images spatially co-registered with grayscale ultrasound (US) images. Fur- thermore, by probing different dark state lifetimes of optically activated contrast agents, multiple mPA “colors” will be simultaneously imaged within tissue. These US-mPA images will display molecular and functional signa- tures of the disease within the structural content of the tissue. The specific objective of this project is to develop an ultrasound-guided modulated photoacoustic imaging approach and demonstrate the developed approach in the background-free detection of micrometastases in sentinel lymph nodes using a murine model of metastatic breast cancer. Indeed, one of the critical components of the clinical cancer management is the analysis of re- gional lymph nodes where current diagnostic methods including imaging suffer from low sensitivity and specificity. Therefore, this US-mPA system will be specifically designed for imaging micrometastases in sentinel lymph nodes. Improved sensitivity and specificity of US-mPA imaging will be demonstrated through synthesis of mo- lecularly targeted contrast agent and coordinated instrumentation development to maximize impact of these new materials and the imaging approach. The successful outcome of this study will enable design and development of a clinical imaging system and contrast agents for background-free molecular imaging of various pathologies.

抽象的 该研究计划的目的是开发一种先进的，无创的，分子特定的成像技术 - NOLODY - 超声引导的调制光声成像增强了，可通过光学活化，有针对性的共同点增强 Trast剂，能够对体内病理的立即，准确，无背景的评估。基础 该项目的假设是光学调制对比剂的超声引导的光声成像 可以实时执行，从而立即提供诊断信息。该方法基于独特 光学活化的分子成像对比剂和相应激光/UL-的组合 TRASOUND成像设备。具体而言，开发高度敏感的成像对比剂，由 二氧化硅纳米颗粒掺有光学活化的光吸光器，并通过抗体功能化涂层 将进行脂质壳。嵌入在二氧化硅芯中的光吸光器暴露于〜50S寿命的瞬态 先前的红色激光照射后，近红外光吸收。对比剂将使用临床对比度进行成像 超声（US）成像系统，与两个（泵/探针）脉冲激光源连接，在任何一个中运行 超声或光声成像模式。泵激光脉冲将反复激活对比剂，因此 允许探针激光脉冲产生可以处理的光声信号，以生成背景 - 自由调制光声（MPA）图像在空间上与灰度超声（US）图像共同注册。毛皮- 热力机，通过探测光学激活的对比剂的不同深色状态寿命，多种MPA“颜色” 将简单地成像在组织中。这些US-MPA图像将显示分子和功能性信号 在组织的结构含量内的疾病。该项目的具体目标是发展 超声引导的调制光声成像方法，并在 使用转移性的鼠模型对哨兵淋巴结中微型转移的无背景检测 乳腺癌。实际上，临床癌症管理的关键组成部分之一是分析重新 当前诊断方法包括敏感性和特异性低的成像，其中的淋巴结淋巴结。 因此，该US-MPA系统将专门设计用于哨兵淋巴中的微型转移 节点。通过合成，将证明提高US-MPA成像的灵敏度和特异性 针对性的对比剂和协调的仪器开发，以最大程度地影响这些新的影响 材料和成像方法。这项研究的成功结果将使设计和开发 用于各种病理的无背景分子成像的临床成像系统和对比剂的。