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Dataset Description
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METHODS: We established a chronic mouse model of CCM, induced by postnatal ablation of Krit1 with Pdgfb-CreERT, and examined lesion progression in these mice with T2-weighted 7T MRI. We also established a modified protocol for dynamic contrast-enhanced (DCE) MRI and produced quantitative maps of gadolinium tracer gadobenate dimeglumine. RESULTS: These mice develop CCM lesions gradually over 4-5 months of age throughout the brain. Precise volumetric analysis of individual lesions revealed non-monotonous behavior, with some lesions temporarily growing smaller. However, the cumulative lesional volume invariably increased over time, and after about 2 months followed a power trend. Using DCE MRI, we produced quantitative maps of gadolinium in the lesions, indicating a high degree of heterogeneity in lesional permeability. Animals and Treatments All animal experiments were approved by the Animal Care and Use Committee at the University of Virginia. To generate experimental animals, male Pdgfb-CreERT mice were crossed to the floxed and null Krit1 alleles (Krit1fl/null) to produce the desired genotype Pdgfb-CreERT; Krit1 fl/null males or females. Krit1 gene ablation was induced with a single subcutaneous injection of 50uL of tamoxifen dissolved in corn oil at a concentration of 2 mg/mL between postnatal day 5 and 7. MR Imaging A 7T small animal MRI scanner (Bruker/Siemens ClinScan) was used to acquire T2-SPACE and T1 contrast images. Mice were imaged monthly, starting as early as one month of age and as late as 5 months of age. To be included in this study, each animal had to have at least two imaging time points conducted. Three-dimensional T2-SPACE MRIs were acquired for all mice in this study using a repetition time of 3000 ms, echo time of 80 ms, pixel size of 125 μm x 125 μm x 100 μm, and 2 averages. Scan time for the T2-SPACE sequence was ~20 min. T1 contrast mapping was executed by performing 3D spoiled gradient echo sequences at various flip angles before, and 5 minutes after, gadolinium contrast injection, including the following flip angles: 1, 2, 4, 8, 12, 20, and 30°. All sequences in this series had a repetition time of 10 ms, echo time of 2.6 ms, pixel size of 187.5 μm x 187.5 μm x 200 μm, and 1 average. The scan time for the total image series (pre and post contrast injection combined) was ~20 minutes. To initially determine the optimal time to acquire the post-gadolinium image series such that gadolinium accumulation is maximized and time is minimized, the post-series was repeated every 4 minutes following gadolinium injection up to 20 minutes. Gadolinium contrast (MultiHance) was injected as a bolus intravenously with a dose of 0.01 mmol diluted in saline at a molarity of 0.2mmol/mL.
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