Neonatal Hypoxic-ischemic Brain Damage In Piglets Comparison Of Apparent Diffusion Coefficients,Proton MR Spectroscopy And Histopathology

Purpose To compare the apparent diffusion coefficients (ADCs), proton magnetic resonance spectroscopy (~1H-MRS), pathologic changes and heat shock protein 70 (HSP70) expression in young pigs subjected to acute hypoxic-ischemic brain damage (HIBD). Thus, to investigate the practical value of the two MR modalities in evaluating hypoxic-ischemic encephalopathy (HIE). Materials and Methods Twenty-five 7-day-old neonatal pigs were subjected to permanent bilateral common carotid arteries occlusion followed by ventilation with 4% oxygen for 1 hour. Diffusion-weighted imaging (DWI) and ~1H-MRS were performed on cessation of the insult (n=5), 3 hours after resuscitation (n=5), 6 hours after resuscitation (n=5), 12 hours after resuscitation (n=5), or 24 hours after resuscitation (n=5). ADCs and peak-height ratios of different brain metabolites were calculated, including N-acetylaspartate/choline (NAA/Cho), NAA/creatine (NAA/Cr), lactate/NAA (Lac/NAA), Lac/Cho and Lac/Cr. Immediately after MR examinations, injury of the brains was evaluated by hematoxylin-eosin-stained pathologic study and HSP70 immunohistochemical expression analysis. Fifteen sham-operation control piglets were divided into three groups. They underwent the above MR and histopathologic studies on cessation of the insult (n=5), 12 hours after resuscitation (n=5) or 24 hours after resuscitation (n=5). Results The experimental piglets showed ADC reduction, Lac peak, Lac/Cho and Lac/Cr increase on cessation of the insult, progressive ADC reduction, Lac peak, Lac/Cho and Lac/Cr decrease after resuscitation, and ADC augment, Lac peak, Lac/Cho and Lac/Cr increase 24 hours after the insult. The area of foci on ADC maps approximately showed a progressively decreasing tendency. NAA peak, NAA/Cho and NAA/Cr demonstrated reduction on cessation of the insult, transient recovery 3 hours after the insult and gradual reduction from 3 to 24 hours after resuscitation. Pathologic study revealed swelling of astrocytes, perivascular space dilation and microvascular congestion more and more severe after resuscitation. Immunohistochemical examination depicted no HSP70-positive cells on cessation of the insult, gradual increase from 3 to 12 hours after resuscitation and decrease 24 hours after the insult. The control piglets showed normal MR and histopathologic investigations. No HSP70 positive expression cells were seen. Conclusions The changes of ADCs, NAA, Cho and Lac can sensitively reflect the injury degree of brain cells in the early phase of HIE. The ratio of NAA/Cho can directly reflect thepathological changes of the early cerebral hypoxic-ischemic damage. A combination of HSP70 immunohistochemical expression, ADC value, ratios of NAA/Cho, Lac/NAA, Lac/Cho and Lac/Cr has great value on delineating the injury degree of HIBD and evaluating the injury penumbra in HI foci. It is of great significance for clinicians to establish the therapeutic window and evaluate the injury degree, therapeutic effects and long-term prognosis of HI neonates.