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: 10172901
• 负责人: ROBERT M DICKSON
• 金额: $ 59.1万
• 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/10172901
• 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; Structure; 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

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 该研究计划的目标是开发一种先进的、非侵入性的、分子特异性成像技术 nology – 超声引导调制光声成像，通过光学激活、有针对性的con-增强 治疗剂，能够对体内病理进行即时、准确、无背景的评估。 该项目的假设是光学调制造影剂的超声引导光声成像 可以实时执行，产生即时诊断信息。 光激活分子靶向成像造影剂和相应激光/ul-的组合 具体来说，开发了一种高灵敏度成像造影剂，其组成为 掺杂有光学激活光吸收剂并涂有抗体功能化的二氧化硅纳米颗粒 嵌入二氧化硅核心的光吸收剂表现出〜50μs的短暂寿命。 先前的红色激光照射后的近红外光学吸收将使用临床成像。 超声（美国）成像系统，与两个（泵/探头）脉冲激光源连接，可在任一模式下运行 超声或光声成像模式中泵浦激光脉冲将重复激活造影剂，从而 允许探测激光脉冲产生光声信号，该信号可以被处理以产生背景 自由调制光声 (mPA) 图像与灰度超声 (US) 图像在空间上共同配准。 thermore，通过探测光激活造影剂的不同暗态寿命，多种 mPA“颜色” 这些 US-mPA 图像将同时在组织内成像，显示分子和功能信号。 该项目的具体目标是开发组织结构内容内的疾病特征。 超声引导调制光声成像方法并展示了所开发的方法 使用小鼠转移模型对前哨淋巴结中的微转移进行无背景检测 事实上，临床癌症管理的关键组成部分之一是重新分析。 目前的诊断方法（包括影像学）的敏感性和特异性较低。 因此，该 US-mPA 系统将专门设计用于前哨淋巴微转移成像 US-mPA 成像的灵敏度和特异性的提高将通过 mo- 的合成来证明。 眼球靶向造影剂和协调仪器开发，以最大限度地发挥这些新的影响 这项研究的成功结果将使设计和开发成为可能。 用于各种病理的无背景分子成像的临床成像系统和造影剂。