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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.

非常需要开发新的非侵入性成像方法来检测细菌感染提高特异性和时空分辨率。尽管迄今为止已经有许多分子成像方法已被证明可以用于临床前动物模型中的细菌感染，临床兼容的成像方法与传统标记的需求之间显然存在差距策略，通常需要使用金属或放射性造影剂。为了解决这一差距，我们正在开发一种“非标记”（即无放射性、非顺磁或超顺磁）检测细菌的方法。在这种方法中，细菌细胞通过其使用称为化学交换饱和的创新 MRI 技术来检测内源性分子转机（欧洲中部夏令时间）。我们研究的长期目标是利用这种内源性细菌特异性 CEST MRI信号可检测病原菌并监测细菌感染的进展。和最初一样在实体瘤中得到证实，我们表明 CEST MRI 可以检测治疗性细菌 C. novyi-NT，一种转基因细菌菌株，目前正处于治疗实体瘤的一期临床试验中。基于根据初步数据，我们假设 CEST MRI 可以检测萌发和增殖 C. novyi-NT 可用作预测溶菌成功的非侵入性成像生物标志物神经胶质瘤的治疗，一种高度致命的脑肿瘤类型。我们计划通过完成以下任务来检验我们的假设以下两个具体目标： 1）使用新方法提高细菌 CEST 对比的特异性开发了 CEST 技术，以及 2) 测试和验证优化的细菌 CEST MRI 检测 C. novyi-NT 癌症疗法。我们预计，实现这些目标将带来高度专门用于细菌检测的可翻译 MRI 技术，可立即用作 C.novyi-NT 溶菌疗法临床试验中的影像生物标志物。更重要的是，从该项目中获得的知识将能够进一步扩展拟议的 CEST MRI 的使用检测许多其他类型细菌的方法，这对于脑等深部器官细菌感染的诊断和治疗监测目前很难检测到。

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.

使用化学交换饱和转移在水溶液中检测和定量过氧化氢。