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¹H and hyperpolarized ³He magnetic resonance imaging clearly detect the preventative effect of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo

Olsson, Lars E LU ; Smailagic, Amir; Onnervik, Per-Ola; Lindén, Anders and Hockings, Paul D (2011) In Innate Immunity 17(2). p.11-204
Abstract

INTRODUCTION: Proton (¹H ) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) ³He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of ¹H and HP ³He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.

MATERIALS AND METHODS: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the... (More)

INTRODUCTION: Proton (¹H ) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) ³He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of ¹H and HP ³He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.

MATERIALS AND METHODS: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty-eight hours after the aerosol exposure, the mice were anaesthetized for subsequent imaging. Hyperpolarized ³He was administered and axial MR images of the lungs obtained. Matching ¹H MR images were then acquired. The mice were sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine total and cell differential counts.

RESULTS: The lesion volume on both ¹H and ³He MRI, were markedly increased by endotoxin exposure (P<0.001). Budesonide strongly reduced lesion volume (P<0.001). The BAL cell count correlated strongly with both (3)He (P<0.001; r = 0.96) and ¹H lesion volumes (P<0.001; r = 0.97).

CONCLUSIONS: Hyperpolarized ³He MRI and ¹H MRI clearly visualized the preventative effect of budesonide on the impact of endotoxin on pulmonary ventilation and edema, respectively. The fact that ventilation defects on ³He MRI corresponded to findings from conventional ¹H MRI, as well as to counts of BAL inflammatory cells suggests that these imaging techniques constitute promising tools for non-invasive monitoring of pulmonary inflammation in vivo.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Bronchoalveolar Lavage Fluid, Budesonide, Endotoxins, Feasibility Studies, Helium, Hydrogen, Magnetic Resonance Imaging, Mice, Mice, Inbred BALB C, Pneumonia, Respiratory Function Tests
in
Innate Immunity
volume
17
issue
2
pages
8 pages
publisher
SAGE Publications
external identifiers
  • Scopus:79953694794
ISSN
1753-4267
DOI
10.1177/1753425909359191
language
English
LU publication?
no
id
32d75e5b-8d59-4903-b53a-af16ef3e5484
date added to LUP
2016-08-16 12:10:40
date last changed
2016-10-13 05:12:16
@misc{32d75e5b-8d59-4903-b53a-af16ef3e5484,
  abstract     = {<p>INTRODUCTION: Proton (¹H ) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) ³He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of ¹H and HP ³He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.</p><p>MATERIALS AND METHODS: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty-eight hours after the aerosol exposure, the mice were anaesthetized for subsequent imaging. Hyperpolarized ³He was administered and axial MR images of the lungs obtained. Matching ¹H MR images were then acquired. The mice were sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine total and cell differential counts.</p><p>RESULTS: The lesion volume on both ¹H and ³He MRI, were markedly increased by endotoxin exposure (P&lt;0.001). Budesonide strongly reduced lesion volume (P&lt;0.001). The BAL cell count correlated strongly with both (3)He (P&lt;0.001; r = 0.96) and ¹H lesion volumes (P&lt;0.001; r = 0.97).</p><p>CONCLUSIONS: Hyperpolarized ³He MRI and ¹H MRI clearly visualized the preventative effect of budesonide on the impact of endotoxin on pulmonary ventilation and edema, respectively. The fact that ventilation defects on ³He MRI corresponded to findings from conventional ¹H MRI, as well as to counts of BAL inflammatory cells suggests that these imaging techniques constitute promising tools for non-invasive monitoring of pulmonary inflammation in vivo.</p>},
  author       = {Olsson, Lars E and Smailagic, Amir and Onnervik, Per-Ola and Lindén, Anders and Hockings, Paul D},
  issn         = {1753-4267},
  keyword      = {Animals,Bronchoalveolar Lavage Fluid,Budesonide,Endotoxins,Feasibility Studies,Helium,Hydrogen,Magnetic Resonance Imaging,Mice,Mice, Inbred BALB C,Pneumonia,Respiratory Function Tests},
  language     = {eng},
  number       = {2},
  pages        = {11--204},
  publisher    = {ARRAY(0x9ab62a8)},
  series       = {Innate Immunity},
  title        = {¹H and hyperpolarized ³He magnetic resonance imaging clearly detect the preventative effect of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo},
  url          = {http://dx.doi.org/10.1177/1753425909359191},
  volume       = {17},
  year         = {2011},
}