Optimal parameters for near infrared fluorescence imaging of amyloid plaques in Alzheimer's disease mouse models.
Amyloid-beta plaques are an Alzheimer's disease biomarker which present unique challenges for near-infrared fluorescence tomography because of size (<50 microm diameter) and distribution. We used high-resolution simulations of fluorescence in a digital Alzheimer's disease mouse model to investigate the optimal fluorophore and imaging parameters for near-infrared fluorescence tomography of amyloid plaques. Fluorescence was simulated for amyloid-targeted probes with emission at 630 and 800 nm, plaque-to-background ratios from 1-1000, amyloid burden from 0-10%, and for transmission and reflection measurement geometries. Fluorophores with high plaque-to-background contrast ratios and 800 nm emission performed significantly better than current amyloid imaging probes. We tested idealized fluorophores in transmission and full-angle tomographic measurement schemes (900 source-detector pairs), with and without anatomical priors. Transmission reconstructions demonstrated strong linear correlation with increasing amyloid burden, but underestimated fluorescence yield and suffered from localization artifacts. Full-angle measurements did not improve upon the transmission reconstruction qualitatively or in semi-quantitative measures of accuracy; anatomical and initial-value priors did improve reconstruction localization and accuracy for both transmission and full-angle schemes. Region-based reconstructions, in which the unknowns were reduced to a few distinct anatomical regions, produced highly accurate yield estimates for cortex, hippocampus and brain regions, even with a reduced number of measurements (144 source-detector pairs).
Raymond
S B
SB
The Harvard-MIT Division of Health Sciences and Technology, 77 Mass Ave., E25-519, Cambridge, MA 02139, USA.
Kumar
A T N
AT
Boas
D A
DA
Bacskai
B J
BJ
D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000473:pathology; D002138:Calibration; D004195:Disease Models, Animal; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D015233:Models, Statistical; D055095:Optics and Photonics; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013055:Spectrophotometry, Infrared / Q000379:methods*
D016229:Amyloid beta-Peptides