title: Noninvasive imaging of infection after treatment with tumor-homing bacteria using Chemical Exchange Saturation Transfer (CEST) MRI.
abstract: OBJECTIVE
  To develop a noninvasive MRI method for determining the germination and infection of tumor-homing bacteria in bacteriolytic cancer therapy using endogenous CEST contrast.
  
  
  METHODS
  The CEST parameters of the anaerobic gram-positive bacterium Clostridium novyi-NT (C. novyi-NT) were first characterized in vitro, then used to detect C. novyi-NT germination and infection in subcutaneous CT26 colorectal tumor-bearing mice (n = 6) after injection of 300 million bacterial spores. Lipopolysacharide (LPS) injected mice were used to exclude that the changes of CEST MRI were due to inflammation.
  
  
  RESULTS
  CEST contrast was observed over a broad frequency range for bacterial suspensions in vitro, with the maximum contrast around 2.6 ppm from the water resonance. No signal could be detected for bacterial spores, demonstrating the specificity for germination. In vivo, a significant elevation of CEST contrast was identified in C. novyi-NT infected tumors as compared to those before bacterial germination and infection (P < 0.05; n = 6). No significant change was observed in tumors with LPS-induced sterile inflammation (P > 0.05; n = 4).
  
  
  CONCLUSIONS
  Endogenous bacterial CEST contrast (bacCEST) can be used to monitor the germination and proliferation of the therapeutic bacterium C. novyi-NT without a need for exogenous cell labeling probes.
authors.affiliation: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Guanshu
authors.initials: G
authors.lastname: Liu
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Verena
authors.initials: V
authors.lastname: Staedtke
authors.forename: Kannie W Y
authors.initials: KW
authors.lastname: Chan
authors.forename: Renyuan
authors.initials: R
authors.lastname: Bai
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Li
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
authors.forename: Assaf A
authors.initials: AA
authors.lastname: Gilad
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Shibin
authors.initials: S
authors.lastname: Zhou
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods; D045744:Cell Line, Tumor; D003013:Clostridium / Q000302:isolation & purification* / Q000502:physiology*; D003015:Clostridium Infections / Q000382:microbiology / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: CEST MRI; bacteria imaging; endogenous CEST contrast; molecular imaging