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

Abstract

Purpose: To develop a new MRI method to detect and characterize brain abscesses using the CEST contrast inherently carried by bacterial cells, namely bacCEST.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: CEST; MRI; bacterial infection; brain abscess.

Figure 1. CEST MRI detection of Staphylococcus aureus (S. aureus)

a) Z-spectra and b) MTR_asym plots of S. aureus and Clostridium novyi-NT and PBS; c) MRI images and CEST parametric maps at 2.6 ppm showing the test tubes containing S. aureus, C. novyi-NT and PBS. The concentrations of S. aureus and C. novyi-NT were 2×10⁸ and 2×10⁷ cells/ml in PBS solution (pH 7.4), respectively. All CEST data were acquired using a 3-sec long CW RF pulse (B₁=3.6 μT) at 37 °C

Figure 2. CEST MRI of brain abscess

a) T_2w image of a representative rat brain with a bacterial abscess on the 12th day after implantation, with the lesion indicated by the yellow arrow. b) H&E stain (4x). c) Gram stain (20x). d) MR spectra of brain abscess (red) and contralateral normal brain tissue (blue) acquired using PRESS (voxel size = 2×2×2 mm³). e) CEST map at 2.6 ppm acquired using B₁=3 μT, t_sat = 3s. f) Z-spectra and g) MTR_asym plots (mean± sd) of ROIs encompassing the brain abscess (red) and contralateral normal brain tissue (blue). g) Comparison of the CEST contrasts in abscess and contralateral brain (n=8).

Figure 3. Differentiation of brain abscess from F98 brain tumor using dual-B₁ CEST MRI

a) T_2w image showing the bacterial abscess and the tumor as indicated by arrows. b) CEST map at 2.6 ppm acquired using B₁=3 μT. c) MTR_asym map at 2.6 ppm acquired using B₁=1 μT. d) ΔCEST map calculated from MTR_asym (B₁=3 μT) - MTR_asym (B₁=1 μT). ROI-based MTR_asym plots of abscess, tumor and brain using e) B₁= 3 μT and f) B₁=1 μT. g) B₁-dependence of CEST signal of abscesses (n=4), F98 tumors (n=4), and 9L tumors (n=3) at 2.6 ppm offset. h) Bar plots of the mean ΔMTR_asym(2.6ppm, 3μT - 1μT) of abscesses (n=4), F98 tumors (n=4), and 9L tumors (n=3).

Figure 4. CEST MRI monitoring the treatment response of bacteria

a) T_2w images showing the location of bacterial abscesses (arrows) and the corresponding CEST maps (overlaid on T_2w images) of a representative ampicillin-treated brain-abscess-bearing rat at different time points. b) Scatter plots of mean ROI MTR_asym values of abscesses of three rats at different time points after the antibiotic treatment. c) T_2w images and CEST maps of a representative untreated brain-abscess-bearing rat at different time points. d) Scatter plots of mean ROI MTR_asym values of abscesses of three rats at different time points after the antibiotic treatment. e) Comparison of the bacCEST signal of treated and untreated rats at day 4 and day 10. The bacCEST signals were normalized by the signal on day 0.