Optimization of CEST MRI for detection of bacteria

高度期望开发新的非侵入性成像方法用于检测细菌感染， 改进的特异性和时空分辨率。尽管到目前为止有许多分子 成像方法已在临床前动物模型中证明可用于细菌感染， 显然，临床兼容成像方法和传统标记的需求之间存在差距 这通常需要使用金属或放射性造影剂。为了弥补这一差距，我们 正在开发“非标记”（即，非放射性，非顺磁性或超顺磁性） 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， 转移（CEST）。本研究的长期目标是利用这种内源性细菌特异性CEST MRI信号检测病原菌和监测细菌感染的进展。如最初 在实体瘤中证实，我们表明CEST MRI可以检测治疗性细菌C。诺维-NT， 一种目前正在进行治疗实体瘤的I期临床试验的转基因菌株。基于 根据初步的数据，我们假设CEST MRI可以检测到细胞的萌发和增殖， C. novyi-NT可用作预测溶菌成功的非侵入性成像生物标志物。 神经胶质瘤是一种高致命性的脑肿瘤。我们计划通过完成 具体有两个目的：1）利用新的CEST技术提高细菌CEST对比的特异性 开发的CEST技术，和2）为了测试和验证优化的细菌CEST MRI检测， 梭novyi-NT癌症疗法。我们预计，实现这些目标将导致一个高度 专门用于细菌检测的可平移MRI技术，可立即用作 诺氏梭菌-NT溶菌疗法临床试验中的成像生物标志物。更重要的是 从该项目中获得的知识将使拟议的CEST MRI的使用得到进一步扩展 方法来检测许多其他类型的细菌，这将是非常有用的 诊断和治疗监测细菌感染的深部器官，如大脑， 目前难以检测。

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.