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.

摘要