Hybrid FMT-CT imaging of amyloid-beta plaques in a murine Alzheimer's disease model.
The need to study molecular and functional parameters of Alzheimer's disease progression in animal models has led to the development of disease-specific fluorescent markers. However, curved optical interfaces and a highly heterogeneous internal structure make quantitative fluorescence imaging of the murine brain a particularly challenging tomographic problem. We investigated the integration of X-ray computed tomography (CT) information into a state-of-the-art fluorescence molecular tomography (FMT) scheme and establish that the dual-modality approach is essential for high fidelity reconstructions of distributed fluorescence within the murine brain, as compared to conventional fluorescence tomography. We employ this method in vivo using a fluorescent oxazine dye to quantify amyloid-beta plaque burden in transgenic APP23 mice modeling Alzheimer's disease. Multi-modal imaging allows for accurate signal localization and correlation of in vivo findings to ex vivo studies. The results point to FMT-CT as an essential tool for in vivo study of neurodegenerative disease in animal models and potentially humans.
Hyde
Damon
D
Laboratory for Bio-optics and Molecular Imaging, Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. dhyde@ece.neu.edu
de Kleine
Ruben
R
MacLaurin
Sarah A
SA
Miller
Eric
E
Brooks
Dana H
DH
Krucker
Thomas
T
Ntziachristos
Vasilis
V
D000544:Alzheimer Disease / Q000175:diagnosis*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology*; D013382:Subtraction Technique; D014057:Tomography, X-Ray Computed / Q000379:methods*