Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment

Sepideh Shokouhi; John W Mckay; Suzanne L Baker; Hakmook Kang; Aaron B Brill; Harry E Gwirtsman; William R Riddle; Daniel O Claassen; Baxter P Rogers; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1186/s13195-016-0172-3

Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment

Alzheimers Res Ther. 2016 Jan 15:8:2. doi: 10.1186/s13195-016-0172-3.

Authors

Sepideh Shokouhi¹, John W Mckay², Suzanne L Baker³, Hakmook Kang⁴, Aaron B Brill⁵, Harry E Gwirtsman⁶, William R Riddle⁷, Daniel O Claassen⁸, Baxter P Rogers⁹; Alzheimer’s Disease Neuroimaging Initiative

Collaborators

Alzheimer’s Disease Neuroimaging Initiative:
Michael W Weiner, Paul Aisen, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R Jack Jr, William Jagust, John Q Trojanowki, Arthur W Toga, Laurel Beckett, Robert C Green, Andrew J Saykin, John Morris, Leslie M Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Robert C Green, Tom Montine, Ronald Petersen, Paul Aisen, Ronald G Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B Balasubramanian, Jennifer Mason, Iris Sim, Laurel Beckett, Danielle Harvey, Michael Donohue, Clifford R Jack Jr, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, William Jagust, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C Morris, Nigel J Cairns, Erin Householder, Lisa Taylor-Reinwald, Leslie M Shaw, John Q Trojanowki, Virginia Lee, Magdalena Korecka, Michal Figurski, Arthur W Toga, Karen Crawford, Scott Neu, Andrew J Saykin, Tatiana M Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Michael W Weiner, Lean Thal, Zaven Khachaturian, Leon Thal, Neil Buckholtz, Michael W Weiner, Peter J Snyder, William Potter, Steven Paul, Marylyn Albert, Richard Frank, Zaven Khachaturian, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L Heidebrink, Joanne L Lord, Ronald Petersen, Sara S Mason, Colleen S Albers, David Knopman, Kris Johnson, Rachelle S Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S Honig, Karen L Bell, Beau Ances, John C Morris, Maria Carroll, Mary L Creech, Erin Franklin, Mark A Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik Roberson, Marissa Natelson Love, Hillel Grossman, Effie Mitsis, Raj C Shah, Leyla deToledo-Morrell, Ranjan Duara, Daniel Varon, Maria T Greig, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Daniel D'Agostino 2nd, Stephanie Kielb, James E Galvin, Brittany Cerbone, Christina A Michel, Dana M Pogorelec, Henry Rusinek, Mony J de Leon, Lidia Glodzik, Susan De Santi, P Murali Doraiswamy, Jeffrey R Petrella, Salvador Borges-Neto, Terence Z Wong, Edward Coleman, Steven E Arnold, Jason H Karlawish, David Wolk, Christopher M Clark, Charles D Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L Lopez, MaryAnn Oakley, Donna M Simpson, Anton P Porsteinsson, Bonnie S Goldstein, Kim Martin, Kelly M Makino, M Saleem Ismail, Connie Brand, Ruth A Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I Levey, James J Lah, Janet S Cellar, Jeffrey M Burns, Russell H Swerdlow, William M Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H S Silverman, Po H Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Tracy Kendall, Heather Johnson, Martin R Farlow, Ann Marie Hake, Brandy R Matthews, Jared R Brosch, Scott Herring, Cynthia Hunt, Christopher H van Dyck, Richard E Carson, Martha G MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A Sperling, Keith A Johnson, Gad Marshall, Jerome Yesavage, Joy L Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N Sabbagh, Christine M Belden, Sandra A Jacobson, Sherye A Sirrel, Neil Kowall, Ronald Killiany, Andrew E Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M Carlsson, Steven G Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Anna Burke, Nadira Trncic, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W Scharre, Maria Kataki, Anahita Adeli, Earl A Zimmerman, Dzintra Celmins, Alice D Brown, Godfrey D Pearlson, Karen Blank, Karen Anderson, Laura A Flashman, Marc Seltzer, Mary L Hynes, Robert B Santulli, Kaycee M Sink, Leslie Gordineer, Jeff D Williamson, Pradeep Garg, Franklin Watkins, Brian R Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J Rosen, Bruce L Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Elizabether Finger, Stephen Pasternak, Irina Rachinsky, John Rogers, Andrew Kertesz, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K Schultz, Laura L Boles Ponto, Hyungsub Shim, Karen Ekstam Smith, Norman Relkin, Gloria Chaing, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Michael W Weiner, Paul Aisen, Michael Weiner, Paul Aisen, Ronald Petersen, Robert C Green, Danielle Harvey, Clifford R Jack Jr, William Jagust, John C Morris, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowki, Thomas Neylan, Jordan Grafman, Robert C Green, Tom Montine, Michael Weiner, Ronald Petersen, Paul Aisen, Ronald G Thomas, Michael Donohue, Devon Gessert, Tamie Sather, Melissa Davis, Rosemary Morrison, Gus Jiminez, Thomas Neylan, Jacqueline Hayes, Shannon Finley, Danielle Harvey, Michael Donohue, Clifford R Jack Jr, Matthew Bernstein, Bret Borowski, Jeff Gunter, Matt Senjem, Kejal Kantarci, Chad Ward, William Jagust, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Susan Landau, John C Morris, Nigel J Cairns, Erin Householder, Leslie M Shaw, John Q Trojanowki, Virginia Lee, Magdalena Korecka, Michal Figurski, Arthur W Toga, Karen Crawford, Scott Neu, Andrew J Saykin, Tatiana M Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Michael W Weiner, Karl Friedl, Lon S Schneider, Sonia Pawluczyk, Mauricio Beccera, James Brewer, Helen Vanderswag, Yaakov Stern, Lawrence S Honig, Karen L Bell, Debra Fleischman, Konstantinos Arfanakis, Raj C Shah, Ranjan Duara, Daniel Varon, Maria T Greig, P Murali Doraiswamy, Jeffrey R Petrella, Olga James, Anton P Porsteinsson, Bonnie Goldstein, Kimberly S Martin, Ruth A Mulnard, Gaby Thai, Catherine McAdams-Ortiz, Jacobo Mintzer, Dino Massoglia, Olga Brawman-Mintzer, Carl Sadowsky, Walter Martinez, Teresa Villena, William Jagust, Susan Landau, Howard Rosen, David Perry, Raymond Scott Turner, Kelly Behan, Brigid Reynolds, Reisa A Sperling, Keith A Johnson, Gad Marshall, Marwan N Sabbagh, Sandra A Jacobson, Sherye A Sirrel, Thomas O Obisesan, Saba Wolday, Joanne Allard, Sterling C Johnson, J Jay Fruehling, Sandra Harding, Elaine R Peskind, Eric C Petrie, Gail Li, Jerome A Yesavage, Joy L Taylor, Ansgar J Furst, Steven Chao, Norman Relkin, Gloria Chaing, Lisa Ravdin

Affiliations

¹ Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN, 37232-2310, USA. [email protected].
² Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN, 37232-2310, USA. [email protected].
³ Center of Functional Imaging, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA, 94720, USA. [email protected].
⁴ Department of Biostatistics, Vanderbilt University, 2525 West End Avenue, 11th Floor, Suite 11000, Nashville, TN, 37203-1738, USA. [email protected].
⁵ Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN, 37232-2310, USA. [email protected].
⁶ Department of Psychiatry, Vanderbilt University, 1601 23rd Avenue South, Nashville, TN, 37212, USA. [email protected].
⁷ Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN, 37232-2310, USA. [email protected].
⁸ Department of Neurology, Vanderbilt University, A-0118 Medical Center North, 1161 21st Avenue South, Nashville, TN, 37232-2551, USA. [email protected].
⁹ Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN, 37232-2310, USA. [email protected].

Abstract

Background: Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-β (Aβ) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test-retest (18)F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions.

Methods: We calculated the correlation between (18)F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ1-42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique-the weighted two-point correlation function (wS2)-to capture potentially more subtle changes in Aβ-PET data.

Results: Compared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF Aβ1-42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS2 values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aβ1-42 levels across all time points and reference regions, including the cerebellar gray matter.

Conclusions: The selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical (18)F-florbetapir uptake in longitudinal studies.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Amyloid beta-Peptides / cerebrospinal fluid*
Aniline Compounds
Brain / diagnostic imaging
Brain / metabolism*
Cognitive Dysfunction / cerebrospinal fluid
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / metabolism*
Ethylene Glycols
Female
Humans
Longitudinal Studies
Male
Peptide Fragments / cerebrospinal fluid*
Positron-Emission Tomography / methods*
Reference Standards
Reproducibility of Results

Substances

Amyloid beta-Peptides
Aniline Compounds
Ethylene Glycols
Peptide Fragments
amyloid beta-protein (1-41)
florbetapir

Abstract

Publication types

MeSH terms

Substances

Grants and funding