A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging.
BACKGROUND
Early detection of hypoxic-ischemic (HI) injury in the asphyxic newborn is important because present prognostic factors are inadequate. Furthermore, therapeutic interventions may have additional benefit if initiated in time.


OBJECTIVE
To assess whether the use of a combined protocol including conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and proton MR spectroscopy (MRS) could detect pathological findings in a piglet model 7 hours after HI.


METHODS
Ten piglets were submitted to HI for 30 min followed by reoxygenation with 21% O2 for 7 hours. MRI at 1.5T was done prior to and 7 hours after the HI. Single-voxel proton MRS was performed, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in the basal ganglia. MRS identified N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac). Histology and microtubule-associated protein 2 (MAP-2) staining was performed in the basal ganglia at the end of the experiment.


RESULTS
Compared to baseline, ADC, NAA/Cho, and NAA/Cr were significantly reduced after 7 hours (P<0.001, P=0.01, and P=0.05, respectively) and FA values were increased (P<0.025). The ratios of Lac/Cho and Lac/NAA were significantly higher after 7 hours compared to baseline (P<0.001). Presence of necrosis correlated well with reduced ADC (R(S)=0.91) and presence of Lac (R(S)=0.80). Histology and MAP-2 staining showed more than 90% necrosis in eight piglets, 60% in one piglet, and no necrosis in one piglet.


CONCLUSIONS
Diffusion MRI and proton MRS can detect HI injury in the piglet brain 7 hours after hypoxia. DWI and MRS can be used to give useful prognostic information. This piglet model may potentially be used to mimic clinical situations and is suitable for further research investigating HI injury.
Munkeby
B H
BH
Department of Paediatric Research, Institute for Surgical Research, Rikshospitalet University Hospital, Oslo, Norway.
De Lange
C
C
Emblem
K E
KE
Bjørnerud
A
A
Kro
G A B
GA
Andresen
J
J
Winther-Larssen
E H
EH
Løberg
E M
EM
Hald
J K
JK
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001479:Basal Ganglia / Q000737:chemistry; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002794:Choline / Q000032:analysis; D003401:Creatine / Q000032:analysis; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis*; D019344:Lactic Acid / Q000032:analysis; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008869:Microtubule-Associated Proteins / Q000032:analysis; D013552:Swine
D008869:Microtubule-Associated Proteins; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline