A Semiautomated Method for Quantification of F 18 Florbetapir PET Images.
PET amyloid imaging is increasingly used in research trials related to Alzheimer disease and has potential as a quantitative biomarker. This study had 3 objectives: first, to describe a semiautomated quantitative method that does not require subject-specific MR imaging scans for estimating F 18 Florbetapir plaque binding using 10-min PET images; second, to evaluate the method's accuracy for identifying positive and negative scans; and third, to correlate derived standardized uptake value ratios to neuropathologic measures of amyloid.


METHODS
The F 18 Florbetapir PET images are initially converted to Montreal Neurologic Institute brain atlas space using an internally developed PET target F 18 Florbetapir template. Subsequently, a single mean cortical standardized uptake value ratio (mcSUVr) is calculated from the mean standardized uptake value of 6 cortical regions normalized to a reference region. Four reference regions were explored: whole cerebellum, cerebellar gray matter, pons, and centrum semiovale. The performance of the resultant mcSUVrs were evaluated in 74 young cognitively normal subjects (age < 50 y) with a negligible likelihood of amyloid β pathology, and in 59 deceased subjects with autopsy-based amyloid β neuritic plaque measure who underwent F 18 Florbetapir PET imaging before death.


RESULTS
Significant correlations were obtained between mcSUVrs and 3 different pathologic measures of amyloid deposition at autopsy using all 4 reference regions, with the whole-cerebellum mcSUVr correlating most strongly across pathologic measures (r = 0.71-0.75, P < 0.0001). Using the whole-cerebellum mcSUVr and a threshold mcSUVr of less than 1.10, 100% of young cognitively normal subjects were correctly classified as amyloid-negative (mcSUVr range, 0.87-1.08). Similarly, 20 of 20 autopsy-negative subjects showed mcSUVrs of 1.10 or less, whereas 38 of 39 pathology-verified amyloid-positive subjects had mcSUVrs of more than 1.10.


CONCLUSIONS
This semiautomated F 18 Florbetapir PET quantification method yielded mcSUVrs that significantly correlated with measures of amyloid pathology at autopsy. The method also effectively discriminated autopsy-identified amyloid-positive and -negative cases using a whole-cerebellum mcSUVr threshold of 1.10.
Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania joshi@avidrp.com.
Abhinay D
AD
Joshi
Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania.
Michael J
MJ
Pontecorvo
Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania.
Ming
M
Lu
Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania.
Daniel M
DM
Skovronsky
Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania.
Mark A
MA
Mintun
Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania.
Michael D
MD
Devous
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D058227:Amyloidogenic Proteins / Q000378:metabolism; D000686:Amyloidosis / Q000000981:diagnostic imaging / Q000473:pathology; D000814:Aniline Compounds; D001331:Automation; D001344:Autopsy; D001921:Brain / Q000000981:diagnostic imaging; D002531:Cerebellum / Q000000981:diagnostic imaging; D005026:Ethylene Glycols; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011149:Pons / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods* / Q000706:statistics & numerical data; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results
D058227:Amyloidogenic Proteins; D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir
Alzheimer’s; PET; florbetapir; neuropathology; quantification