MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation

PLoS One. 2016 May 26;11(5):e0154705. doi: 10.1371/journal.pone.0154705. eCollection 2016.

Abstract

Purpose: To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection.

Methods: S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique.

Results: Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine.

Conclusion: Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines.

Publication types

  • Evaluation Study

MeSH terms

  • Abscess* / diagnostic imaging
  • Abscess* / immunology
  • Abscess* / microbiology
  • Administration, Intravenous
  • Animals
  • Female
  • Kidney Diseases* / diagnostic imaging
  • Kidney Diseases* / immunology
  • Kidney Diseases* / microbiology
  • Kidney* / diagnostic imaging
  • Kidney* / immunology
  • Kidney* / microbiology
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Inbred BALB C
  • Staphylococcal Infections* / diagnosis
  • Staphylococcal Infections* / immunology
  • Staphylococcal Vaccines / immunology*
  • Staphylococcal Vaccines / pharmacokinetics
  • Staphylococcus aureus / immunology*

Substances

  • Staphylococcal Vaccines

Grants and funding

The research leading to these results has received funding from the European Union's Seventh Framework Programme under the grant agreement n° 601783 (BELLEROPHON project, to DW) and 316655 (VACTRAIN) (CL). The research was supported in part by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford (to DW). JES is a BHF Senior Basic Science Research Fellow (FS/11/50/29038). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CR is a Jenner Institute Investigator and an Oxford Martin fellow. Imaxio SA provided support in the form of salaries for FH but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.