Optimization of CEST MRI for detection of bacteria

用于细菌检测的 CEST MRI 优化

基本信息

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
项目类别：
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

项目摘要

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。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Detecting acid phosphatase enzymatic activity with phenol as a chemical exchange saturation transfer magnetic resonance imaging contrast agent (PhenolCEST MRI).

DOI：
10.1016/j.bios.2019.111442
发表时间：
2019-09
期刊：
Biosensors & bioelectronics
影响因子：
12.6
作者：
Jia Zhang;Yue Yuan;Zheng Han;Yuguo Li;P. V. van Zijl;Xing Yang;J. Bulte;Guanshu Liu
通讯作者：
Jia Zhang;Yue Yuan;Zheng Han;Yuguo Li;P. V. van Zijl;Xing Yang;J. Bulte;Guanshu Liu

Detection and Quantification of Hydrogen Peroxide in Aqueous Solutions Using Chemical Exchange Saturation Transfer.