Optimization of CEST MRI for detection of bacteria

迫切需要开发一种新的非侵入性成像方法来检测细菌感染 提高了特异性和时空分辨率。尽管到目前为止有许多分子 在临床前动物模型中，已经证明了细菌感染的成像方法。 显然，临床兼容成像方法的需求与传统标记之间存在差距 战略，这往往需要使用金属或放射性造影剂。为了解决这一差距，我们 正在发展一种“非标记的”(即无放射性，也不是顺磁性或超顺磁性的) 检测细菌的方法。在这种方法中，细菌细胞直接通过它们的 使用一种名为化学交换饱和的创新磁共振技术的内源分子 转账(CEST)。我们研究的长期目标是开发这种内源性细菌特有的CEST MRI信号检测病原菌，监测细菌感染进展。和最初一样 在实体瘤中验证，我们发现CEST MRI可以检测到一种治疗性细菌C.novyi-NT， 一种目前处于治疗实体瘤的第一阶段临床试验的转基因细菌菌株。基座 根据初步数据，我们假设CEST MRI检测到的是 C.novyi-NT可作为预测溶菌成功与否的非侵入性影像标志物 治疗胶质瘤，一种高致命性的脑瘤类型。我们计划通过完成 目的：1)提高细菌CEST对比试验的特异性 开发CEST技术，以及2)测试和验证优化的细菌CEST MRI检测 新冠癌症疗法。我们预计实现这些目标将带来高度的 专门用于细菌检测的可翻译MRI技术，可立即用作 新诺氏杆菌溶菌治疗临床试验中的成像生物标志物。更重要的是， 从这个项目中获得的知识将使拟议的CEST MRI的使用进一步扩大 许多其他类型的细菌的检测方法，这将对 诊断和治疗监测深部器官的细菌感染，如大脑，这些器官是 目前很难检测到。

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.