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Research ArticleBasic Science Investigations

Quantification of β-Amyloidosis and rCBF with Dedicated PET, 7 T MR Imaging, and High-Resolution Microscopic MR Imaging at 16.4 T in APP23 Mice

Florian C. Maier, Marianne D. Keller, Daniel Bukala, Benjamin Bender, Julia G. Mannheim, Ian M. Brereton, Graham J. Galloway and Bernd J. Pichler
Journal of Nuclear Medicine October 2015, 56 (10) 1593-1599; DOI: https://doi.org/10.2967/jnumed.115.159350
Florian C. Maier
1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
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Marianne D. Keller
2University of Queensland, Centre for Advanced Imaging, Brisbane, Australia
3South Australian Health and Medical Research Institute, Adelaide, Australia; and
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Daniel Bukala
1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
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Benjamin Bender
4Department for Neuroradiology, University Hospital Tübingen, Tübingen, Germany
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Julia G. Mannheim
1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
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Ian M. Brereton
2University of Queensland, Centre for Advanced Imaging, Brisbane, Australia
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Graham J. Galloway
2University of Queensland, Centre for Advanced Imaging, Brisbane, Australia
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Bernd J. Pichler
1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
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  • FIGURE 1.
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    FIGURE 1.

    Quantification of amyloid burden with 11C-PIB PET and amyloid histology. (A) Transversal, horizontal, and sagittal views of fused 11C-PIB PET/tse3DT2 MR imaging at 7 T of 30-mo-old transgenic APP23 mouse (upper panel) and of age-matched control mouse (lower panel). Note specific 11C-PIB binding in amyloid-affected brain regions of transgenic animal (frontal cortex, hippocampus, temporoparietal cortex, thalamus) in contrast to cerebellum, which is amyloid-unaffected. (B) Quantification of 11C-PIB BPND in transgenic and control mice reveals significantly higher binding in transgenic mice (n = 5) and matches amyloid load assessed by amyloid histology (n = 5). **P < 0.01. FC = frontal cortex; TPC = temporoparietal cortex; Hi = hippocampus ; Th = thalamus.

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    FIGURE 2.

    Correlation of 11C-PIB PET and T2*-weighted microscopic MR imaging at 16.4 T. (A–C) Example of tse3DT2 MR imaging at 7 T (A), corresponding dedicated 11C-PIB PET and MR imaging overlay (B), and respective postmortem T2*-weighted imaging (C) at 16.4 T of same 30-mo-old transgenic APP23 mouse as shown in Figure 1. (D) 11C-PIB BPND and microscopic MR imaging amyloid fractions calculated from T2*-weighted imaging at 16.4 T were correlated linearly (R2 = 0.98, Pearson correlation coefficient; P = 0.99; data are shown for animal presented in A–C and refer to 11C-PIB BPND ± SE of Logan fitting routine and percentage of T2*-weighted amyloid-positive fraction of thalamus, hippocampus, temporoparietal cortex, and frontal cortex). Highres-3DT2*= T2*-weighted.

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    FIGURE 3.

    Correlation of T2*-weighted microscopic MR imaging at 16.4 T and amyloid histology. T2*-weighted image (A) at 16.4 T of 30-mo-old transgenic APP23 mouse and corresponding amyloid histology (B), with matching amyloid plaques are indicated by blue arrowheads. (C) T2*-weighted image at 16.4 T of littermate control APP23 mouse. Only rare hypointensities are present in temporoparietal cortex corresponding to blood vessels parallel to imaging plane or in hippocampus orthogonal to imaging plane (indicated by white arrowheads). Mammillothalamic tract and perifornical nucleus are indicated by red arrowheads. (D) Higher magnification of A and B allows identification of substructures within single amyloid plaques that are related to density of amyloid deposition (blue arrowheads).

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    FIGURE 4.

    Voxel-based correlation of 11C-PIB PET and ASL MR imaging at 7 T. (A and C) Frequency distribution and gaussian fits of 11C-PIB (A) and of rCBF values (C). (B) Example of 2-dimensional voxelwise correlation of 30-mo-old transgenic and littermate control APP23 mouse. Mean ± 2 SD thresholds calculated from A and C are indicated by dashed lines (blue: 11C-PIB thresholds; green: ASL thresholds). This allows assignment of 2-dimensional voxelwise datasets to 4 described gates (indicated by red numbers), gate assignments as percentage for both animals are shown in open numbers (transgenic) and solid numbers (control). (Inset: linear fits to voxelwise correlation plots revealed inverse correlation of 11C-PIB and rCBF in transgenic APP23 mice; littermate controls displayed no such correlation (n = 5, P < 0.05)). (D) Two-dimensional voxel-value probability distribution of all transgenic and control APP23 mice (shown is voxel distribution in 4 gates as percentage).

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Journal of Nuclear Medicine: 56 (10)
Journal of Nuclear Medicine
Vol. 56, Issue 10
October 1, 2015
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Quantification of β-Amyloidosis and rCBF with Dedicated PET, 7 T MR Imaging, and High-Resolution Microscopic MR Imaging at 16.4 T in APP23 Mice
Florian C. Maier, Marianne D. Keller, Daniel Bukala, Benjamin Bender, Julia G. Mannheim, Ian M. Brereton, Graham J. Galloway, Bernd J. Pichler
Journal of Nuclear Medicine Oct 2015, 56 (10) 1593-1599; DOI: 10.2967/jnumed.115.159350

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Quantification of β-Amyloidosis and rCBF with Dedicated PET, 7 T MR Imaging, and High-Resolution Microscopic MR Imaging at 16.4 T in APP23 Mice
Florian C. Maier, Marianne D. Keller, Daniel Bukala, Benjamin Bender, Julia G. Mannheim, Ian M. Brereton, Graham J. Galloway, Bernd J. Pichler
Journal of Nuclear Medicine Oct 2015, 56 (10) 1593-1599; DOI: 10.2967/jnumed.115.159350
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Keywords

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