Optimization of CEST MRI for detection of bacteria

用于细菌检测的 CEST MRI 优化

• 批准号: 9303352
• 负责人: Guanshu Liu
• 金额: $ 8.08万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303352
• 关键词: Address; Amides; Amination; Amines; Anaerobic Bacteria; Animal Model; Animals; Antineoplastic Agents; Bacteria; Bacterial Infections; Bifidobacterium; Bone Marrow; Brain; Brain Neoplasms; Cell Survival; Cells; Cessation of life; Characteristics; Chemicals; Clinical; Clinical Trials; Clostridium; Contrast Media; Data; Detection; Development; Diagnosis; Environment; Escherichia; Event; Experimental Autoimmune Encephalomyelitis; Experimental Neoplasms; Frequencies; Germination; Glioma; Goals; Growth; Hour; Hydroxyl Radical; Hypoxia; Imaging technology; Infection; Inflammation; Inflammatory; Injectable; Injection of therapeutic agent; Investigation; Kinetics; Knowledge; Label; Lesion; Magnetic Resonance Imaging; Measures; Medical; Methods; Mission; Modeling; Monitor; Morbidity - disease rate; Organ; Pathology; Phase I Clinical Trials; Physiologic pulse; Protocols documentation; Protons; Public Health; Radioactive; Reporting; Reproduction spores; Research; Resolution; Salmonella; Signal Transduction; Solid Neoplasm; Specificity; Techniques; Technology; Technology Transfer; Testing; Therapeutic; Time; Treatment Efficacy; United States National Institutes of Health; Water; base; bioluminescence imaging; cancer therapy; clinical application; clinical practice; clinically translatable; human disease; imaging agent; imaging approach; imaging biomarker; imaging modality; improved; innovation; interest; metallicity; molecular imaging; mortality; neoplastic cell; non-invasive imaging; novel; novel therapeutics; pathogen; pathogenic bacteria; pre-clinical; predictive marker; success; temporal measurement; tumor; tumor eradication; Address; Amides; Amination; Amines; Anaerobic Bacteria; Animal Model; Animals; Antineoplastic Agents; Bacteria; Bacterial Infections; Bifidobacterium; Bone Marrow; Brain; Brain Neoplasms; Cell Survival; Cells; Cessation of life; Characteristics; Chemicals; Clinical; Clinical Trials; Clostridium; Contrast Media; Data; Detection; Development; Diagnosis; Environment; Escherichia; Event; Experimental Autoimmune Encephalomyelitis; Experimental Neoplasms; Frequencies; Germination; Glioma; Goals; Growth; Hour; Hydroxyl Radical; Hypoxia; Imaging technology; Infection; Inflammation; Inflammatory; Injectable; Injection of therapeutic agent; Investigation; Kinetics; Knowledge; Label; Lesion; Magnetic Resonance Imaging; Measures; Medical; Methods; Mission; Modeling; Monitor; Morbidity - disease rate; Organ; Pathology; Phase I Clinical Trials; Physiologic pulse; Protocols documentation; Protons; Public Health; Radioactive; Reporting; Reproduction spores; Research; Resolution; Salmonella; Signal Transduction; Solid Neoplasm; Specificity; Techniques; Technology; Technology Transfer; Testing; Therapeutic; Time; Treatment Efficacy; United States National Institutes of Health; Water; base; bioluminescence imaging; cancer therapy; clinical application; clinical practice; clinically translatable; human disease; imaging agent; imaging approach; imaging biomarker; imaging modality; improved; innovation; interest; metallicity; molecular imaging; mortality; neoplastic cell; non-invasive imaging; novel; novel therapeutics; pathogen; pathogenic bacteria; pre-clinical; predictive marker; success; temporal measurement; tumor; tumor eradication

It is highly desired to develop new non-invasive imaging approach for detecting bacterial infection with improved specificity and spatial-temporal resolution. Although to date there are a number of molecular imaging approaches have been demonstrated for bacterial infection in the preclinical animal models, there is clearly a gap between the demand of clinically-compatible imaging methods and conventional tagging strategies, which often require the use of metallic or radioactive contrast agents. To address this gap, we are developing a “non-labeled” (i.e., not radioactive, and not paramagnetic- or super-paramagnetic-) approach for detecting bacteria. In this approach bacterial cells are directly detected through their endogenous molecules using an innovative MRI technology called Chemical Exchange Saturation Transfer (CEST). The long-term goal of our research is to exploit this endogenous bacteria-specific CEST MRI signal to detect pathogenic bacteria and monitor the progress of bacterial infection. As initially demonstrated in solid tumors, we showed that CEST MRI could detect a therapeutic bacteria C. novyi-NT, a genetically modified bacteria strain currently in the Phase I clinical trial for treating solid tumors. Based on the preliminary data, we hypothesize that CEST MRI that detects the germination and proliferation of C. novyi-NT can be used as a non-invasive imaging biomarker for predicting the success of bacteriolytic therapy on glioma, a highly lethal brain tumor type. We plan to test our hypothesis through completing the following two specific aims: 1) To improve the specificity of bacterial CEST contrast using newly developed CEST technologies, and 2) To test and validate the optimized bacterial CEST MRI detection in the C. novyi-NT cancer therapy. We anticipate that accomplishing these aims will result in a highly translatable MRI technology specifically for bacterial detection, which could be used immediately as an imaging biomarker in the clinical trials of C.novyi-NT bacteriolytic therapy. More importantly, the knowledge gained from this project will enable a further expansion of using the proposed CEST MRI methods to the detection of many other types of bacteria, which will be enormously useful for the diagnosis and treatment monitoring of bacterial infection in deep organs, such as brain, which are currently difficult to detect.

高度希望开发新的非侵入性成像方法，以检测细菌感染 提高的特异性和时空分辨率。虽然迄今为止有许多分子 在临床前动物模型中，已经证明了对细菌感染的成像方法，那里 显然是临床兼容成像方法的需求与常规标签之间的差距 通常需要使用金属或放射性对比剂的策略。为了解决这个差距，我们 正在开发“未标记”（即不是放射性的，而不是顺磁性或超parmaganetic-） 检测细菌的方法。在这种方法中，细菌细胞通过其直接检测到 内源分子使用创新的MRI技术称为化学交换饱和 转移（CEST）。我们研究的长期目标是利用这种内源性细菌特异性CEST MRI信号检测病原菌并监测细菌感染的进展。最初 在实体瘤中证明，我们表明CEST MRI可以检测到治疗性细菌C. Novyi-NT， 目前在I期临床试验中用于治疗实体瘤的一般细菌菌株。基于 在初步数据上，我们假设CEST MRI检测到发芽和增殖 C. Novyi-NT可以用作预测细菌学成功的非侵入性成像生物标志物 神经胶质瘤治疗，一种高度致命的脑肿瘤类型。我们计划通过完成 以下两个具体的目的：1）使用新近的细菌对比度提高对比度的特异性 开发了CEST技术，以及2）测试和验证优化的细菌CEST CEST MRI检测 C. novyi-NT癌症疗法。我们预计实现这些目标将导致高度 可翻译的MRI技术专门用于细菌检测，可以立即用作 成像生物标志物在c.novyi-NT细菌疗法的临床试验中。更重要的是， 从该项目中获得的知识将使使用拟议的CEST MRI进一步扩展 检测许多其他类型的细菌的方法，这对 深层器官（例如大脑）细菌感染的诊断和治疗监测 目前难以检测。