Imaging mouse lung allograft rejection with (1)H MRI

Magn Reson Med. 2015 May;73(5):1970-8. doi: 10.1002/mrm.25313. Epub 2014 Jun 20.

Abstract

Purpose: To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts.

Methods: Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at postoperative days 3, 7, and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures.

Results: Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 posttransplantation (0.046→0.789; P < 0.05), despite large intermouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003; P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies.

Conclusion: Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment.

Keywords: MRI; acute cellular rejection; compliance; lung transplant.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Allografts
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD4 Antigens / immunology
  • CD8 Antigens / immunology
  • Graft Rejection / immunology
  • Graft Rejection / pathology*
  • Longitudinal Studies
  • Lung / immunology
  • Lung / pathology*
  • Lung Compliance / drug effects
  • Lung Compliance / physiology
  • Lung Transplantation*
  • Magnetic Resonance Imaging / instrumentation*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Organ Size / drug effects
  • Organ Size / physiology

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • CD8 Antigens