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: 10608090
• 负责人: ROBERT M DICKSON
• 金额: $ 57.26万
• 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 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608090
• 关键词: Abbreviations; Acceleration; Algorithms; Antibodies; Area; Binding; Biopsy; Blood; Breast Cancer Model; Breast Melanoma; Cancer Patient; Cardiology; Cells; Clinical; Color; Contrast Media; Coupled; Darkness; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diameter; Disease; Disseminated Malignant Neoplasm; Dyes; Early Diagnosis; Encapsulated; 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; 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; tumor; 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.

摘要 这项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， 超声引导的调制光声成像，由光学激活的靶向对照增强， trast试剂，能够在体内立即、准确、无背景地评估病理学。底层 该项目假设是光学调制造影剂的超声引导光声成像 可以在真实的时间内执行，产生即时的诊断信息。该方法基于独特的 光学可活化的分子靶向成像造影剂和相应的激光/紫外光的组合， 超声波成像装置具体地，开发由以下组成的高灵敏度成像造影剂： 掺杂有可光活化的光吸收剂并涂覆有抗体官能化的 将进行脂质外壳。嵌在二氧化硅芯中的光吸收剂表现出~50 μ s的寿命，瞬态 在先前的红色激光照射下的近红外光吸收。造影剂将使用临床 超声（US）成像系统，与两个（泵浦/探测）脉冲激光源接口，以 超声或光声成像模式。泵浦激光脉冲将反复激活造影剂，因此 允许探测激光脉冲产生光声信号，所述光声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）图像空间共配准。毛皮- 因此，通过探测光学激活造影剂的不同暗态寿命， 将在组织内同时成像。这些US-mPA图像将显示分子和功能信号， 在组织的结构内容内的疾病的特征。该项目的具体目标是开发 一种超声引导的调制光声成像方法，并在 应用转移性淋巴结癌小鼠模型检测前哨淋巴结微转移 乳腺癌事实上，临床癌症管理的关键组成部分之一是分析再- 目前包括成像在内的诊断方法的敏感性和特异性较低。 因此，该US-mPA系统将专门设计用于对前哨淋巴结中的微转移进行成像 结将通过合成单核苷酸单核苷酸，证明US-mPA成像的灵敏度和特异性提高。 有针对性的造影剂和协调的仪器开发，以最大限度地发挥这些新技术的影响 材料和成像方法。这项研究的成功结果将使设计和开发 临床成像系统和造影剂用于各种病理的无背景分子成像。