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

Abstract

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 and 9L 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 = 7) were acquired using 2 B1 values (i.e., 1 and 3 µT) and compared. The bacCEST signal of the brain abscesses in the rats (n = 3) receiving ampicillin (intraperitoneal injection 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 = .003). Moreover, thanks to their different B1 independence, brain abscesses and tumors could be effectively differentiated (p = .005) using ΔCEST(2.6 ppm, 3 µT-1 µT), defined by the difference between the CEST signal (offset = 2.6 ppm) 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 = .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.