title: Modeling clustered activity increase in amyloid-beta positron emission tomographic images with statistical descriptors.
abstract: BACKGROUND
  Amyloid-beta (Aβ) imaging with positron emission tomography (PET) holds promise for detecting the presence of Aβ plaques in the cortical gray matter. Many image analyses focus on regional average measurements of tracer activity distribution; however, considerable additional information is available in the images. Metrics that describe the statistical properties of images, such as the two-point correlation function (S2), have found wide applications in astronomy and materials science. S2 provides a detailed characterization of spatial patterns in images typically referred to as clustering or flocculence. The objective of this study was to translate the two-point correlation method into Aβ-PET of the human brain using 11C-Pittsburgh compound B (11C-PiB) to characterize longitudinal changes in the tracer distribution that may reflect changes in Aβ plaque accumulation.
  
  
  METHODS
  We modified the conventional S2 metric, which is primarily used for binary images and formulated a weighted two-point correlation function (wS2) to describe nonbinary, real-valued PET images with a single statistical function. Using serial 11C-PiB scans, we calculated wS2 functions from two-dimensional PET images of different cortical regions as well as three-dimensional data from the whole brain. The area under the wS2 functions was calculated and compared with the mean/median of the standardized uptake value ratio (SUVR). For three-dimensional data, we compared the area under the wS2 curves with the subjects' cerebrospinal fluid measures.
  
  
  RESULTS
  Overall, the longitudinal changes in wS2 correlated with the increase in mean SUVR but showed lower variance. The whole brain results showed a higher inverse correlation between the cerebrospinal Aβ and wS2 than between the cerebrospinal Aβ and SUVR mean/median. We did not observe any confounding of wS2 by region size or injected dose.
  
  
  CONCLUSIONS
  The wS2 detects subtle changes and provides additional information about the binding characteristics of radiotracers and Aβ accumulation that are difficult to verify with mean SUVR alone.
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Shokouhi
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
authors.forename: Baxter P
authors.initials: BP
authors.lastname: Rogers
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Hakmook
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Claassen
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Mckay
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Riddle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000814:Aniline Compounds; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D015233:Models, Statistical; D049268:Positron-Emission Tomography / Q000379:methods*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D013844:Thiazoles
keywords: 11C-Pittsburgh compound B; amyloid-beta plaques; positron emission tomography; statistical descriptors; two-point correlation function