Evaluation of tumour vascular distribution and function using immunohistochemistry and BOLD fMRI with carbogen inhalation

Clin Radiol. 2016 Dec;71(12):1255-1262. doi: 10.1016/j.crad.2016.04.012. Epub 2016 May 8.

Abstract

Aim: To evaluate oxygenation changes in rat subcutaneous C6 gliomas using blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) combined with non-haemodynamic response function (non-HRF) analysis.

Materials and methods: BOLD fMRI were performed during carbogen inhalation in 20 Wistar rats bearing gliomas. Statistical maps of spatial oxygenation changes were computed by a dedicated non-HRF analysis algorithm. Three types of regions of interest (ROIs) were defined: (1) maximum re-oxygenation zone (ROImax), (2) re-oxygenation zones that were less than the maximum re-oxygenation (ROInon-max), and (3) zones without significant re-oxygenation (ROInone). The values of percent BOLD signal change (PSC), percent enhancement (ΔSI), and significant re-oxygenation (T) were extracted from each ROI. Tumours were sectioned for histology using the fMRI scan orientation and were stained with haematoxylin and eosin and CD105. The number of microvessels (MVN) in each ROI was counted. Differences and correlations among the values for T, PSC, ΔSI, and MVN were determined.

Results: After carbogen inhalation, the PSC significantly increased in the ROImax areas (p<0.01) located in the tumour parenchyma. No changes occurred in any of the ROInone areas (20/20). Some changes occurred in a minority of the ROInon-max areas (3/60) corresponding to tumour necrosis. MVN and PSC (R=0.59, p=0.01) were significantly correlated in the ROImax areas. In the ROInon-max areas, MVN was significantly correlated with PSC (R=0.55, p=0.00) and ΔSI (R=0.37, p=0.00).

Conclusions: Statistical maps obtained via BOLD fMRI with non-HRF analysis can assess the re-oxygenation of gliomas.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Mapping / methods
  • Brain Neoplasms / complications
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / diagnostic imaging
  • Carbon Dioxide / administration & dosage*
  • Disease Models, Animal
  • Female
  • Glioma / complications
  • Glioma / diagnosis*
  • Glioma / diagnostic imaging
  • Hypoxia / complications
  • Hypoxia / diagnosis*
  • Immunohistochemistry
  • Magnetic Resonance Imaging / methods*
  • Male
  • Oxygen / administration & dosage*
  • Radiation-Sensitizing Agents / administration & dosage*
  • Rats
  • Rats, Wistar
  • Respiration

Substances

  • Radiation-Sensitizing Agents
  • Carbon Dioxide
  • carbogen
  • Oxygen