MRI detection of bacterial brain abscesses and monitoring of antibiotic treatment using bacCEST.

To develop a new MRI method to detect and characterize brain abscesses using the CEST contrast inherently carried by bacterial cells, namely bacCEST. Bacteria S. aureus (ATCC #49775) and F98 glioma cells were injected stereotactically in the brains of F344 rats to form abscesses and tumors. The CEST signals of brain abscesses (n=4) and tumors (n=4) were acquired using two B1 values (i.e., 1 and 3 μT) and compared. The bacCEST signal of the brain abscesses in the rats (n=3) receiving ampicillin (i.p. 40 mg/kg twice daily) was acquired before, 4 and 10 days after the treatment. The bacCEST signal of S. aureus was characterized in vitro as a strong and broad signal in the range of 1 to 4 ppm, with the maximum contrast occurring at 2.6 ppm. The CEST signal in S. aureus-induced brain abscesses was significantly higher than that of contralateral parenchyma (P=0.003). Moreover, thanks to their different B1-independece, brain abscesses and tumors could be effectively differentiated (P=0.005) using ΔCEST(2.6ppm,3μT-1μT), defined by the difference between the CEST signal (offset=2.6ppm) acquired using B1 = 3 μT and that of 1 μT. In treated rats, bacCEST MRI could detect the response of bacteria as early as 4 days after the antibiotic treatment (P=0.035). BacCEST MRI provides a new imaging method to detect, discriminate and monitor bacterial infection in deep-seated organs. Because no contrast agent is needed, such an approach has a great translational potential for detecting and monitoring bacterial infection in deep-seated organs.

开发一种新的磁共振成像（MRI）方法，利用细菌细胞固有的化学交换饱和转移（CEST）对比，即细菌CEST（bacCEST）来检测和表征脑脓肿。 将金黄色葡萄球菌（ATCC #49775）和F98胶质瘤细胞立体定向注射到F344大鼠的大脑中以形成脓肿和肿瘤。使用两个B1值（即1微特斯拉和3微特斯拉）获取脑脓肿（n = 4）和肿瘤（n = 4）的CEST信号并进行比较。在接受氨苄西林（腹腔注射，每日两次，每次40mg/kg）治疗的大鼠（n = 3）中，分别在治疗前、治疗后4天和10天获取脑脓肿的bacCEST信号。 金黄色葡萄球菌的bacCEST信号在体外表现为在1至4ppm范围内的强而宽的信号，在2.6ppm处对比度最大。金黄色葡萄球菌诱导的脑脓肿中的CEST信号显著高于对侧脑实质（P = 0.003）。此外，由于它们对B1的依赖性不同，利用ΔCEST(2.6ppm,3μT - 1μT)（由使用B1 = 3μT和1μT获取的CEST信号（偏移量 = 2.6ppm）之间的差值定义）可以有效区分脑脓肿和肿瘤（P = 0.005）。在接受治疗的大鼠中，bacCEST MRI能够早在抗生素治疗后4天检测到细菌的反应（P = 0.035）。 BacCEST MRI提供了一种新的成像方法来检测、区分和监测深部器官中的细菌感染。由于不需要造影剂，这种方法在检测和监测深部器官细菌感染方面具有很大的转化潜力。