Application Of Chemical Exchange Saturation Transfer MRI In Bacterial Brain Abscess And Sepsis-induced Acute Kidney Injury

Purpose(1)To develop a new MRI method to detect and characterize brain abscesses using the CEST contrast inherently carried by bacterial cells,namely bacCEST.(2)To characterize the endogenous Chemical Exchange Saturation Transfer(CEST)MRI contrast in the LPS-induced septic acute kidney injury mouse model and to investigate the use of CEST MRI for detecting such injury.Methods(1)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 3μT)and compared.The bacCEST signal of the brain abscesses in the rats(n=3)receiving amoxicillin(i.p.400 mg/kg daily)was acquired before,4 and 10 days after the treatment.(2)SAKI mouse model that was generated by ip injection of 10 mg/kg LPS.The resulting kidney injury was confirmed by the elevation of serum creatinine and histology.MRI assessments were performed at twenty-four hours after LPS injection,including,CEST MRI at different B1 strengths(1,1.8 and 3 μT),T1 mapping,T2 mapping,and conventional magnetization transfer contrast(MTC)MRI.The CEST MRI results were analyzed using Z-spectra,in which the normalized water signal saturation(Ssat/So)is measured as a function of saturation frequency.Results(1)The bacCEST signal of S.aureus was characterized in vitro as a strong and broad signal in the range of I 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 B,-independece,brain abscesses and tumors could be effectively differentiated(P=0.005)using ACEST(2.6ppm,3μgT-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).(2)Substantial decreases in CEST contrast were observed at both 3.5 and-3.5 ppm frequency offset from water at all B1 powers,with the most significant difference obtained at B1 of 1.8μT.The average Ssat/S0 differences between injured and normal kidneys were 0.07(0.55±0.04 vs 0.62±0.04,P=0.0028)and 0.07(0.50±0.04 vs 0.57±0.03,P=0.0008)for 3.5 and-3.5 ppm,respectively.In contrast,the T1,T2 relaxation times and MTC contrast in the injured kidneys didn’t show a significant change compared to the normal control.ConclusionCEST MRI provides a new imaging method to detect,discriminate and monitor either bacterial infection in deep-seated organs or sepsis induced acute kidney injury(SAKI).Because no contrast agent is needed,such an approach has a great translational potential for detecting and monitoring bacterial infection in deep-seated organs.On the other hand,our results showed that CEST MRI is more sensitive to the pathological changes in injured kidneys prior to the changes in T1,T2 and MT effect,indicating its potential clinical utility for molecular imaging of renal diseases..