Regional difference of cerebral perfusion pressure index in the rat brain: quantitative PET study with ¹⁵O-labeled gas.

Objectives: In the preclinical study, small animal models were often used to evaluate the cerebral blood flow and metabolism. In the steno-occlusive disease of cerebral arteries, it is important to investigate the distribution of regional cerebral perfusion pressure (CPP) index (CBF/CBV) (Gibbs JM, et al. Lancet. 1984) as it is a key determinant of cerebral circulation. The purpose of this study was to evaluate the regional difference of CPP in the normal rat brain by means of ¹⁵O-labeled gas PET. CPP index of CBF/CBV was analyzed.

Methods: Six normal male Sprague-Dawley rats (BW=310.8±19.8 g) were investigated by means of ¹⁵O-labeled gas PET under intramuscular anesthesia with midazolam, xylazine and butorphanol. Cerebral blood flow (CBF) was measured by the steady state inhalation method of 15O-CO₂ gas (400 MBq/min) for 16 min and cerebral blood volume (CBV) was measured by 15O-CO gas (200 MBq/min) for 13 min with arterial blood sampling (Watabe T, et al. J Nucl Med. 2013). PET images were reconstructed by filtered back projection algorithm with attenuation and scatter correction. The PET images were registered in the template of T₂-weighted magnetic resonance image by PMOD software version 3.604. The volumes of interest were automatically placed on the frontal cortex, the somatosensory cortex, the visual cortex, the hippocampus, the striatum, the thalamus, the pons, the midbrain, the cerebellum and the whole brain using the brain atlas template (W.Schiffer). CPP index was calculated as a ratio of CBF to CBV in each brain region and compared among the regions by multiple comparison test followed by Tukey-Kramer HSD test with reference to our previous study in humans (Watabe T, et al. Neurosci Bull. 2014).

Results: Quantitative values were 52.9 ± 10.3 mL/100mL/min for CBF, 5.66 ± 0.34 mL/100mL for CBV and 9.4 ± 2.2 /min for CPP index in the whole brain, respectively. CPP indexes were 7.2 ± 2.2 /min in the frontal cortex, 11.9 ± 2.6 in the somatosensory cortex, 6.9 ± 2.1 in the visual cortex, 13.1 ± 3.5 in the hippocampus, 17.5 ± 3.7 in the striatum, 20.4 ± 4.0 in the thalamus, 10.7 ± 1.8 in the pons, 18.8 ± 3.3 in the midbrain and 9.5 ± 2.7 in the cerebellum, respectively. CPP indexes in the striatum, the thalamus and the midbrain were significantly higher than that in the frontal cortex, the visual cortex and the cerebellum (p < 0.01). Decreased CPP index in the cortex regions and the cerebellum might be due to the effect of anesthesia when compared to our previous study in humans (Watabe T, et al. Neurosci Bull. 2014).

Conclusion: This study demonstrated the regional difference of the cerebral perfusion pressure in normal rat brain by means of ¹⁵O-labeled gas PET. It is essential to consider the regional difference of CPP in the evaluation of steno-occlusive disease model of cerebral arteries. Research Support: None