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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

Logan DVR plot on the cerebellum using the subcortical white matter as reference region (a) and the subcortical white matter using the cerebellum as reference region (b) for the same subjects as shown in Fig. 3. The time point corresponding to the “pseudo” equilibrium (t*=25 min) is also shown
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Fig4: Logan DVR plot on the cerebellum using the subcortical white matter as reference region (a) and the subcortical white matter using the cerebellum as reference region (b) for the same subjects as shown in Fig. 3. The time point corresponding to the “pseudo” equilibrium (t*=25 min) is also shown

Mentions: Figure 3 shows the Logan plots on the frontal cortex for a control subject without specific binding and in a typical AD patient using, respectively, the cerebellum and the subcortical white matter as reference region. The DVR values obtained with either reference region were identical for the control subject and were only slightly lower for the AD patient when the subcortical white matter was used as the reference region. To further demonstrate the similarity in nonspecific binding between the cerebellum and the subcortical white matter, Logan analysis was performed using, respectively, the subcortical white matter and the cerebellum as reference region. Representative results are shown in Fig. 4 for the same subjects shown in Fig. 3. The DVR values obtained for subcortical white matter and the cerebellum using their counterpart as reference region were very close to unity (1.02±0.04 and 0.98±0.05 for control subjects; 1.04±0.03 and 0.96±0.03 for AD patients), indicating that the levels of nonspecific binding in these regions were very similar.Fig. 3


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)

Logan DVR plot on the cerebellum using the subcortical white matter as reference region (a) and the subcortical white matter using the cerebellum as reference region (b) for the same subjects as shown in Fig. 3. The time point corresponding to the “pseudo” equilibrium (t*=25 min) is also shown
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Related In: Results  -  Collection

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

Fig4: Logan DVR plot on the cerebellum using the subcortical white matter as reference region (a) and the subcortical white matter using the cerebellum as reference region (b) for the same subjects as shown in Fig. 3. The time point corresponding to the “pseudo” equilibrium (t*=25 min) is also shown
Mentions: Figure 3 shows the Logan plots on the frontal cortex for a control subject without specific binding and in a typical AD patient using, respectively, the cerebellum and the subcortical white matter as reference region. The DVR values obtained with either reference region were identical for the control subject and were only slightly lower for the AD patient when the subcortical white matter was used as the reference region. To further demonstrate the similarity in nonspecific binding between the cerebellum and the subcortical white matter, Logan analysis was performed using, respectively, the subcortical white matter and the cerebellum as reference region. Representative results are shown in Fig. 4 for the same subjects shown in Fig. 3. The DVR values obtained for subcortical white matter and the cerebellum using their counterpart as reference region were very close to unity (1.02±0.04 and 0.98±0.05 for control subjects; 1.04±0.03 and 0.96±0.03 for AD patients), indicating that the levels of nonspecific binding in these regions were very similar.Fig. 3

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