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.
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 ADpatients. 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 ADpatients. RESULTS: The population estimates of k(')(2) in subcortical white matter did not differ significantly between control subjects and ADpatients 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 ADpatients 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.
Authors: Brian J Lopresti; William E Klunk; Chester A Mathis; Jessica A Hoge; Scott K Ziolko; Xueling Lu; Carolyn C Meltzer; Kurt Schimmel; Nicholas D Tsopelas; Steven T DeKosky; Julie C Price Journal: J Nucl Med Date: 2005-12 Impact factor: 10.057
Authors: Maqsood Yaqub; Nelleke Tolboom; Bart N M van Berckel; Philip Scheltens; Adriaan A Lammertsma; Ronald Boellaard Journal: Neuroimage Date: 2009-07-28 Impact factor: 6.556
Authors: A A Lammertsma; C J Bench; S P Hume; S Osman; K Gunn; D J Brooks; R S Frackowiak Journal: J Cereb Blood Flow Metab Date: 1996-01 Impact factor: 6.200
Authors: Christopher C Rowe; Uwe Ackerman; William Browne; Rachel Mulligan; Kerryn L Pike; Graeme O'Keefe; Henry Tochon-Danguy; Gordon Chan; Salvatore U Berlangieri; Gareth Jones; Kerryn L Dickinson-Rowe; Hank P Kung; Wei Zhang; Mei Ping Kung; Daniel Skovronsky; Thomas Dyrks; Gerhard Holl; Sabine Krause; Matthias Friebe; Lutz Lehman; Stefanie Lindemann; Ludger M Dinkelborg; Colin L Masters; Victor L Villemagne Journal: Lancet Neurol Date: 2008-01-10 Impact factor: 44.182
Authors: Hillary D Protas; Vladimir Kepe; Kiralee M Hayashi; Andrea D Klunder; Meredith N Braskie; Linda Ercoli; Prabha Siddarth; Susan Y Bookheimer; Paul M Thompson; Gary W Small; Jorge R Barrio; Sung-Cheng Huang Journal: Neuroimage Date: 2012-02-28 Impact factor: 6.556
Authors: John M Ringman; Karen H Gylys; Luis D Medina; Michelle Fox; Vladimir Kepe; Deborah L Flores; Liana G Apostolova; Jorge R Barrio; Gary Small; Daniel H Silverman; Erin Siu; Stephen Cederbaum; Silva Hecimovic; Martina Malnar; Suma Chakraverty; Alison M Goate; Thomas D Bird; James B Leverenz Journal: Neurosci Lett Date: 2010-11-19 Impact factor: 3.046
Authors: Michel Koole; June van Aalst; Martijn Devrome; Nathalie Mertens; Kim Serdons; Brigitte Lacroix; Joel Mercier; David Sciberras; Paul Maguire; Koen Van Laere Journal: Eur J Nucl Med Mol Imaging Date: 2018-08-18 Impact factor: 9.236
Authors: Koon-Pong Wong; Vladimir Kepe; Magnus Dahlbom; Nagichettiar Satyamurthy; Gary W Small; Jorge R Barrio; Sung-Cheng Huang Journal: Neuroimage Date: 2011-12-16 Impact factor: 6.556
Authors: Mirwais Wardak; Koon-Pong Wong; Weber Shao; Magnus Dahlbom; Vladimir Kepe; Nagichettiar Satyamurthy; Gary W Small; Jorge R Barrio; Sung-Cheng Huang Journal: J Nucl Med Date: 2010-01-15 Impact factor: 10.057
Authors: H D Protas; S-C Huang; V Kepe; K Hayashi; A Klunder; M N Braskie; L Ercoli; S Bookheimer; P M Thompson; G W Small; J R Barrio Journal: Neuroimage Date: 2009-08-22 Impact factor: 6.556