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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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Representative parametric images of Logan DVR using 125 min of data (with t*=35 min) and white matter as reference input in a control subject (a) and an AD patient (b)
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Fig5: Representative parametric images of Logan DVR using 125 min of data (with t*=35 min) and white matter as reference input in a control subject (a) and an AD patient (b)

Mentions: Parametric DVR images using the white matter as the reference region for a control subject and an AD patient are shown in Fig. 5. The images were generated by applying Logan analysis on a voxel-by-voxel basis to dynamic PET images using data from 0–125 min (t*=35 min). Binding of [18F]FDDNP in the medial temporal, lateral temporal, posterior cingulate, parietal, and frontal regions was much more prominent in the AD patient than in the control subject. Regional DVR values obtained by Logan analysis using different reference regions are shown in Fig. 6. The regional and global DVR values were significantly higher in AD patients in comparison with control subjects. In both study groups, the rank order for DVR estimates was: medial temporal region > posterior cingulate > lateral temporal region > parietal region > frontal region. The same rank order was also observed for DVR estimates obtained with SRTM and SIME-SRTM (data not shown). Regional DVR values obtained using either reference region were related by DVR[white matter as reference region]=0.96 DVR[cerebellum as reference region] (r=0.81, p<0.0001). This linear relation can be derived from the ratio of the specific binding to the nondisplaceable binding using different reference regions (see Appendix).Fig. 5


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)

Representative parametric images of Logan DVR using 125 min of data (with t*=35 min) and white matter as reference input in a control subject (a) and an AD patient (b)
© Copyright Policy
Related In: Results  -  Collection

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

Fig5: Representative parametric images of Logan DVR using 125 min of data (with t*=35 min) and white matter as reference input in a control subject (a) and an AD patient (b)
Mentions: Parametric DVR images using the white matter as the reference region for a control subject and an AD patient are shown in Fig. 5. The images were generated by applying Logan analysis on a voxel-by-voxel basis to dynamic PET images using data from 0–125 min (t*=35 min). Binding of [18F]FDDNP in the medial temporal, lateral temporal, posterior cingulate, parietal, and frontal regions was much more prominent in the AD patient than in the control subject. Regional DVR values obtained by Logan analysis using different reference regions are shown in Fig. 6. The regional and global DVR values were significantly higher in AD patients in comparison with control subjects. In both study groups, the rank order for DVR estimates was: medial temporal region > posterior cingulate > lateral temporal region > parietal region > frontal region. The same rank order was also observed for DVR estimates obtained with SRTM and SIME-SRTM (data not shown). Regional DVR values obtained using either reference region were related by DVR[white matter as reference region]=0.96 DVR[cerebellum as reference region] (r=0.81, p<0.0001). This linear relation can be derived from the ratio of the specific binding to the nondisplaceable binding using different reference regions (see Appendix).Fig. 5

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