Abstract
ObjectiveBrain calcifications are associated with several neurodegenerative diseases. Here, we describe the occurrence of intracranial calcifications as a new phenotype in transgenic P301L mice overexpressing four repeat tau, a model of human tauopathy.Materials and methodsThirty-six P301L mice (Thy1.2) and ten age-matched non-transgenic littermates of different ages were assessed. Gradient echo data were acquired in vivo and ex vivo at 7 T and 9.4 T for susceptibility-weighted imaging (SWI) and phase imaging. In addition, ex vivo micro-computed tomography (μCT) was performed. Histochemistry and immunohistochemistry were used to investigate the nature of the imaging lesions.ResultsSW images revealed regional hypointensities in the hippocampus, cortex, caudate nucleus, and thalamus of P301L mice, which in corresponding phase images indicated diamagnetic lesions. Concomitantly, µCT detected hyperdense lesions, though fewer lesions were observed compared to MRI. Diamagnetic susceptibility lesions in the hippocampus increased with age. The immunochemical staining of brain sections revealed osteocalcin-positive deposits. Furthermore, intra-neuronal and vessel-associated osteocalcin-containing nodules co-localized with phosphorylated-tau (AT8 and AT100) in the hippocampus, while vascular osteocalcin-containing nodules were detected in the thalamus in the absence of phosphorylated-tau deposition.DiscussionSWI and phase imaging sensitively detected intracranial calcifications in the P301L mouse model of human tauopathy.
Highlights
Brain calcification is the most common incidental finding of patients undergoing neuroimaging [1, 2]
In vivo susceptibility-weighted imaging (SWI) and phase imaging at 7 T detect the presence of diamagnetic lesions in brain of P301L mice number of SW/phase diamagnetic deposits increased with age in the hippocampus, but not in the other brain structures (18 months-old vs 3 months-old, p < 0.0001; vs 5 monthsold, p < 0.0001; and vs 9 months-old, p < 0.0001, Fig. 3n)
We collected in vivo gradient recalled echo data of P301L mice and non-transgenic littermates for phase and SWI post-processing (Fig. 1a-d)
Summary
Brain calcification is the most common incidental finding of patients undergoing neuroimaging [1, 2]. Computed tomography (CT) is considered the non-invasive gold standard for the identification of intracranial calcification because it allows discriminating calcification from other sources of focal contrast (hemorrhagic lesions or infarctions). It is estimated that 20% of aged individuals have brain calcifications, where they are detected in the pineal gland and choroid plexus [1, 2]. Magnetic resonance imaging (MRI) is the preferred imaging modality for assessing the central nervous system because of its high soft-tissue contrast and because it does not use ionizing radiation. Unequivocal identification of intracranial calcifications with MRI is challenging. On conventional T1-, T2-weighted spin-echo MR images calcifications appear
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