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

Wong KP, Wardak M, Shao W, Dahlbom M, Kepe V, Liu J, Satyamurthy N, Small GW, Barrio JR, Huang SC - Eur. J. Nucl. Med. Mol. Imaging (2009)

Bottom Line: 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.The DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly higher in the AD group (p<0.01).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.

View Article: PubMed Central - PubMed

Affiliation: 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. kpwong@ucla.edu

ABSTRACT

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Related in: MedlinePlus

Effect of variation in  in white matter on the accuracy of DVRs derived by Logan graphical analysis in control subjects (a) and AD patients (b). Variations in DVR in the frontal region (FRT), parietal region (PAR), medial temporal region (MTL), lateral temporal region (LTL), and posterior cingulate (PCG) were determined using an assumed  value of 0.023 min−1
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Fig9: Effect of variation in in white matter on the accuracy of DVRs derived by Logan graphical analysis in control subjects (a) and AD patients (b). Variations in DVR in the frontal region (FRT), parietal region (PAR), medial temporal region (MTL), lateral temporal region (LTL), and posterior cingulate (PCG) were determined using an assumed value of 0.023 min−1

Mentions: Figure 9 shows the effect of the value of on the accuracy of DVRs derived by Logan analysis. All regions exhibited a similarly large dependence on the value of in both control subjects and AD patients. Varying the value of from −80% to +100% above the population value of 0.023 min−1 resulted in variations in the regional DVR values varied from −19.7% to +3.1% in control subjects (Fig. 9a) and from −21.2% to +3.4% in AD patients (Fig. 9b) over their means and the DVR values were more susceptible to negative bias in the value. Increasing tenfold (which covered a wide range of plausible values) or eliminating the term from the calculation of DVR resulted in a variation ranging from +1.5% to +7.1% in all regions examined.Fig. 9


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

Wong KP, Wardak M, Shao W, Dahlbom M, Kepe V, Liu J, Satyamurthy N, Small GW, Barrio JR, Huang SC - Eur. J. Nucl. Med. Mol. Imaging (2009)

Effect of variation in  in white matter on the accuracy of DVRs derived by Logan graphical analysis in control subjects (a) and AD patients (b). Variations in DVR in the frontal region (FRT), parietal region (PAR), medial temporal region (MTL), lateral temporal region (LTL), and posterior cingulate (PCG) were determined using an assumed  value of 0.023 min−1
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2822232&req=5

Fig9: Effect of variation in in white matter on the accuracy of DVRs derived by Logan graphical analysis in control subjects (a) and AD patients (b). Variations in DVR in the frontal region (FRT), parietal region (PAR), medial temporal region (MTL), lateral temporal region (LTL), and posterior cingulate (PCG) were determined using an assumed value of 0.023 min−1
Mentions: Figure 9 shows the effect of the value of on the accuracy of DVRs derived by Logan analysis. All regions exhibited a similarly large dependence on the value of in both control subjects and AD patients. Varying the value of from −80% to +100% above the population value of 0.023 min−1 resulted in variations in the regional DVR values varied from −19.7% to +3.1% in control subjects (Fig. 9a) and from −21.2% to +3.4% in AD patients (Fig. 9b) over their means and the DVR values were more susceptible to negative bias in the value. Increasing tenfold (which covered a wide range of plausible values) or eliminating the term from the calculation of DVR resulted in a variation ranging from +1.5% to +7.1% in all regions examined.Fig. 9

Bottom Line: 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.The DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly higher in the AD group (p<0.01).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.

View Article: PubMed Central - PubMed

Affiliation: 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. kpwong@ucla.edu

ABSTRACT

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus