Quantitative analysis of [F-18]FDDNP PET using subcortical white matter as reference region

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Rm. B2-085E CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
European Journal of Nuclear Medicine (Impact Factor: 5.38). 10/2009; 37(3):575-88. DOI: 10.1007/s00259-009-1293-8
Source: PubMed


Subcortical white matter is known to be relatively unaffected by amyloid deposition in Alzheimer's disease (AD). We investigated the use of subcortical white matter as a reference region to quantify [(18)F]FDDNP binding in the human brain.
Dynamic [(18)F]FDDNP PET studies were performed on 7 control subjects and 12 AD patients. Population efflux rate constants (k(')(2)) from subcortical white matter (centrum semiovale) and cerebellar cortex were derived by a simplified reference tissue modeling approach incorporating physiological constraints. Regional distribution volume ratio (DVR) estimates were derived using Logan and simplified reference tissue approaches, with either subcortical white matter or cerebellum as reference input. Discriminant analysis with cross-validation was performed to classify control subjects and AD patients.
The population estimates of k(')(2) in subcortical white matter did not differ significantly between control subjects and AD patients but the variability of individual estimates of k(')(2) determined in white matter was lower than that in cerebellum. Logan DVR showed dependence on the efflux rate constant in white matter. The DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly higher in the AD group (p<0.01). Incorporating all these regional DVR estimates as predictor variables in discriminant analysis yielded accurate classification of control subjects and AD patients with high sensitivity and specificity, and the results agreed well with those using the cerebellum as the reference region.
Subcortical white matter can be used as a reference region for quantitative analysis of [(18)F]FDDNP with the Logan method which allows more accurate and less biased binding estimates, but a population efflux rate constant has to be determined a priori.

Download full-text


Available from: Weber Shao, Dec 23, 2014
  • Source
    • "Therefore, the RE plot approach would produce systematically lower DVR estimates in those regions when t* is not long enough (e.g., t* ≤ 45 min), as the linearity of the curve is not yet achieved (Fig. 7). This is different from the Logan graphical analysis, in which the linearity of the plot is normally attained before the true steadystate equilibrium is reached (Logan et al., 1990, 1996; Wong et al., 2010). The suppression of DVR values in the scalp and the blood vessel regions, however, was no longer apparent when a longer t* Fig. 7. Representative Logan (A,C) and RE (B,D) plots for internal carotid artery, scalp, frontal cortex, and subcortical white matter in a patient diagnosed with AD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Logan graphical analysis with cerebellum as reference region has been widely used for the estimation of the distribution volume ratio (DVR) of [18F]FDDNP as a measure of amyloid burden and tau deposition in human brain because of its simplicity and computational ease. However, spurious parametric DVR images may be produced with shorter scanning times and when the noise level is high. In this work, we have characterized a relative-equilibrium-based (RE) graphical method against the Logan analysis for parametric imaging and region-of-interest (ROI) analysis.
    Full-text · Article · Dec 2011 · NeuroImage
  • [Show abstract] [Hide abstract]
    ABSTRACT: Positron emission tomography (PET) with 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malo-nonitrile ([18F]FDDNP) has been used for in vivo imaging of ?-amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease (AD). Due to its simplicity as compared to other reference tissue modeling methods, Logan graphical analysis with cerebellum as reference region has been primarily used to estimate the distribution volume ratio (DVR) of [18F]FDDNP as a measure of amyloid burden and tau deposition in human brain. However, it sometimes produces spurious parametric DVR images when the noise level is high and the total scan duration is shortened. The purpose of this study was to characterize a new graphical analysis method against the Logan analysis for the estimation of the DVR estimates at regional and voxel-wise levels, using the cerebellum as the reference region. Effects on regional (frontal and medial temporal) DVR estimates and parametric DVR images obtained by the Logan and the new approaches using data in different time intervals and total scan durations (35-125 min, 65-125 min, 85-125 min, and 45-65 min) were investigated and compared to the reference values derived by the Logan analysis for the time interval 35-125 min. For regional analyses, with the exception of DVR estimates of medial temporal in ADs obtained by the Logan analysis for the interval 85-125 min, no significant difference was observed for all paired comparisons with the reference values. Logan DVR images generated using shortened time intervals (85-125 min and 45-65 min) were extremely noisy. In contrast, the new method produced DVR images comparable to the reference images even when shortened time intervals were used. The new method provides more reliable regional DVR estimates and less noisy parametric images, indicating that it is an improvement over the Logan graphical analysis for analyzing [18F]FDDNP PET data.
    No preview · Article · Jan 2009 · IEEE Nuclear Science Symposium conference record. Nuclear Science Symposium
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess quantitatively the cortical pattern profile of regional FDDNP binding to beta-amyloid and neurofibrillary tangles on MR derived cortical maps, FDDNP PET images were corrected for movement and partial volume (PV), and optimized for kernel size. FDDNP DVR PET images from 23 subjects (7 with Alzheimer's disease (AD), 6 with mild cognitive impairment and 10 controls) were obtained from Logan analysis using cerebellum as reference. A hemispheric cortical surface model for each subject was extracted from the MRI. The same transformations were applied to the FDDNP DVR PET images to map them into the same space. The cortical map with PV correction was calculated as the ratio of the DVR cortical surface and that of the simulated map, created from the mask derived from MRI and smoothed to the PET resolution. Discriminant analysis was used to order the FDDNP DVR cortical surfaces based on subjects' disease state. Linear regression was used to assess the rate of change of DVR vs. MMSE for each hemispheric cortical surface point. The FDDNP DVR cortical surface corrected for movement and PV had less hemispheric asymmetry. Optimal kernel size was determined to be 9 mm. The corrected cortical surface map of FDDNP DVR showed clear spatial pattern that was consistent with the known pathological progression of AD. Correcting for movement, PV as well as optimizing kernel size provide sensitive statistical analysis of FDDNP distribution which confirms in the living brain known pathology patterns earlier observed with cognitive decline with brain specimens.
    Full-text · Article · Sep 2009 · NeuroImage
Show more