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


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.
Olsson
Lars E
LE
DECS/Imaging, AstraZeneca R&D Mölndal, Mölndal, Sweden. lars.e.olsson@astrazeneca.com
Smailagic
Amir
A
Onnervik
Per-Ola
PO
Lindén
Anders
A
Hockings
Paul D
PD
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology; D019819:Budesonide / Q000008:administration & dosage; D004731:Endotoxins / Q000008:administration & dosage; D005240:Feasibility Studies; D006371:Helium / Q000008:administration & dosage* / Q000737:chemistry; D006859:Hydrogen / Q000008:administration & dosage* / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D012129:Respiratory Function Tests
D004731:Endotoxins; D006371:Helium; D019819:Budesonide; D006859:Hydrogen