Simultaneous PET and MRI during hypoxic challenge in mouse cerebral hypoxia-ischemia

Objectives Recent developments in small animal integrated PET/MRI have allowed new possibilities in preclinical imaging [1-3]. In the cerebral hypoxia-ischemia (H-I) model, changes in physiological parameters during and shortly after hypoxia occur on the order of minutes [4]. Here, we demonstrate the use of a novel integrated PET/MRI device to measure parameters of interest from both modalities simultaneously and at a fine temporal resolution.

Methods Our group has developed a 7T MRI-compatible PET insert based on position-sensitive avalanche photodiodes, with a 6 cm axial FOV and spatial resolution of 1.25 mm. Animals (male C57BL/6 mice, 8-10 weeks, n=6) received right common carotid artery ligation. After 3-7 hours of recovery, a baseline diffusion weighted image (DWI) was acquired (echo planar sequence, z-axis diffusion, b=0, 400, and 800 s²/mm). PET acquisition was then started with a constant infusion (4.44 µL/min, 411±32 µCi) of [¹⁸F]FDG. After 10 minutes, animals underwent a 30 minute hypoxic challenge (8% O₂, 92% N₂). During this time, two additional DWI scans were acquired (hypoxia 1 and 2). A final DWI scan was acquired after restoration of normoxia. Parameters of interest from left and right hemispheres were compared. The apparent diffusion coefficient (ADC) was calculated by fitting to a single exponential decay.

Results (See Fig.) We observed a trend of decreasing ADC in the right hemisphere relative to the left that is consistent with literature [4]. The mean % left-right difference (%LR) at baseline, hypoxia 1, hypoxia 2, and normoxia was -1.5±2, 7.2±8, 16±10, and 28±8, respectively. The mean %LR in [¹⁸F]FDG uptake was 11% (n=3, %LR > 0 in two animals) during hypoxia 2.

Conclusions We have demonstrated concurrent measurement of PET and MRI parameters of interest in cerebral H-I. Longitudinal imaging using simultaneous PET/MRI is ideally suited to the study of acute brain injury due to the fast evolution of the pathophysiology and the high variability of the animal model.

Research Support This work was funded in part by NIH Grant R01 EB000993.