Abstract
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Objectives Neurofibromatosis type 1 is a single-gene disorder affecting neurologic function in humans. The NF1+/- mouse model with a germline mutation of the NF1 gene presents with deficits in learning, attention and motor coordination, very similar to NF1 patients. Brain perfusion SPECT with Tc-99m-HMPAO was performed in NF1 and wildtype (WT) mice in order to identify possible perfusion differences as surrogate marker for altered cerebral activity in NF1.
Methods Thirty-nine mice were included, 20 NF1 and 19 WT. HMPAO was injected into a tail vein after i.p. anesthesia. A static SPECT of 40 min duration was started 10 min p.i. using a nanoSPECT/CT equipped with general purpose mouse apertures (1.2kcps/MBq, FWHM=0.7mm). A baseline SPECT was obtained between 5 and 9 weeks of age, a follow-up scan at 13-23 weeks. The 3-D MRI Digital Atlas Database of an Adult C57BL/6J Mouse Brain was used for ROI analysis. SPECT images were stereotactically normalized using SPM8 and a custom made, left-right symmetric HMPAO template in atlas space. Voxel intensities were scaled to global uptake.
Results Multivariate testing revealed increased HMPAO uptake in the amygdala (p=0.005) and the olfactory bulb (p=0.004) in NF1 mice at baseline. At follow-up, there was no NF1 effect on HMPAO uptake averaged over both hemispheres (p=0.327). NF1 mice showed significantly larger left-right asymmetry in the superior colliculi both at baseline (p=0.009) and follow-up (p=0.003), with larger HMPAO uptake in the right hemisphere (asymmetry index -1.8±4.6 and -4.5±4.5% at baseline and follow-up).
Conclusions NF1 mice have abnormal perfusion pattern compared to their WT littermates with different characteristics according to age. Altered perfusion in the amygdala is in agreement with previous studies suggesting a role of this brain region in neurologic deficits in NF1 mice