Test-retest reproducibility of [18F]FPEB
Online Resource
RESULTS
Comparison of 2T, MA1, and EQ for BPND
BPND results, using cerebellar white matter (CWM) as reference, by three different analyses
methods are shown in Online Resource Table S1. By any method, anterior cingulate cortex had
the highest BPND among the ROIs examined. BPND estimated by different methods agreed well
with each other (Online Resource Figure S1). BPND estimated by MA1 had excellent correlation
with BPND estimated by 2T (BPND (MA1) = 0.96  BPND (2T), r2 = 0.98). BPND estimated by EQ90-120
had good correlation with BPND estimated by 2T (BPND (EQ90-120) = 0.89  BPND (2T), r2 = 0.90),
although EQ90-120 underestimated BPND in all ROIs by a mean of 11%. The intersubject
variability values measured by mean CoV across the ROIs were 13.5% for 2T, 13.8% for MA1,
and 16.5% for EQ (blood data are not used in calculation of BPND from equilibrium data). When
BPND was estimated using cerebellar grey matter (CGM) as a reference region, mean BPND was
lower, with values ranging from 29% to 48% of the values calculated using CWM as a reference.
Test-retest variability (TRV) of BPND
Mean TRV of BPND, using CWM as reference, ranged from -1% to 4% for 2T, from 0% to 4%
for MA1, and from -4% to 2% for EQ90-120 across the ROIs. Mean TRV of all ROIs were
comparable for the three analyses. SD of TRV ranged from 10% to 19% for 2T, 9% to 14% for
MA1, and 14% to 21% for EQ90-120. Mean aTRV ranged from 7% to 14% for 2T, 6% to 11% for
MA1, and 9% to 15% for EQ90-120. MA1 provided the smallest values for SD of TRV and aTRV
compared to the other analyses, but the numbers were close to each other. 2T, MA1 and EQ90-120
1
Test-retest reproducibility of [18F]FPEB
provided excellent ICC values, which were comparable to each other, with values ranging from
0.81 to 0.96 across the ROIs. Detailed results for each ROI are shown in Online Resource Table
S2.
When comparing TRV values of BPND calculated using CGM as a reference region (Online
Resource Table S3) to those obtained using CWM as a reference, mean TRV with CGM was
similar to that with CWM for all analysis methods. The SD of TRV was also similar between the
two for kinetic analyses, but the SD of TRV was smaller for BPND with CGM than that with
CWM for EQ (mean of SD of TRV across the ROIs: 8% vs. 18%). The poorer SD of TRV with
BPND from CWM can be attributed to a combination of more variability in equilibrium in CWM
(due to slower kinetics in the white matter), and poorer statistics in the smaller size of the CWM
region. In the pallidum, the mean and SD of TRV and mean aTRV were larger with CGM than
with CWM, because VT of the pallidum was only slightly higher than that of CGM, thus the
mean value of BPND for pallidum was substantially reduced.
EQ analysis of BPND using various time windows
Earlier time windows than 90-120 min p.i. were used to estimate BPND by EQ, to test if scanning
could be moved forward. Time windows of 80-110 min, 70-100 min, and 60-90 min were
examined. Even BPND estimated using 60-90 min p.i. data demonstrated excellent correlation
with BPND 90-120 (BPND 60-90 = 0.90 · BPND 90-120, r2 = 0.93). The percent difference of 60-90 vs.
90-120 min values was +8% ± 8%. Shorter time windows were also evaluated to test if scanning
time could be shortened. Fifteen-minute time windows of 105-120 min, 90-105 min, 75-90 min,
and 60-75 min were tried. The correlation with BPND 90-120 was excellent even for BPND 60-75
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Test-retest reproducibility of [18F]FPEB
(BPND 60-75 = 0.87 · BPND 90-120, r2 = 0.95, Online Resource Figure S2). The percent difference of
60-75 vs. 90-120 min values was +12% ± 6%. Both earlier and shorter time windows
underestimated BPND in all ROIs by a mean of up to 13% than 90-120 min, but did not make the
TRV of [18F]FPEB less reproducible. For example, the mean TRV, SD of TRV and mean of
aTRV were -3%, 15%, 11% for BPND 60-90 and -4%, 14%, and 12% for BPND 60-75, compared
to -1%, 18%, and 12% for BPND 90-120.
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Test-retest reproducibility of [18F]FPEB
TABLES
Online Resource Table S1. BPND results by different analysis methods using cerebellar white matter
(CWM) as a reference region.
ROI
2T
MA1 (t*=30)
EQ (90-120 min)
anterior cingulate
4.4 ± 0.5
4.2 ± 0.5
3.8 ± 0.6
posterior cingulate
1.9 ± 0.5
1.9 ± 0.5
1.8 ± 0.5
frontal
3.1 ± 0.4
3.0 ± 0.4
2.9 ± 0.5
temporal
3.9 ± 0.6
3.7 ± 0.5
3.3 ± 0.6
parietal
3.2 ± 0.6
3.0 ± 0.6
2.9 ± 0.7
occipital
3.0 ± 0.6
2.9 ± 0.6
2.8 ± 0.6
hippocampus
3.2 ± 0.5
3.1 ± 0.4
2.5 ± 0.5
caudate nucleus
3.5 ± 0.4
3.4 ± 0.4
3.1 ± 0.5
putamen
3.6 ± 0.4
3.5 ± 0.4
3.3 ± 0.5
pallidum
1.6 ± 0.2
1.6 ± 0.2
1.5 ± 0.2
thalamus
2.0 ± 0.3
2.0 ± 0.3
2.0 ± 0.4
Numbers are mean ± standard deviation (SD).
BPND values were calculated using cerebellar white matter as a reference region and averaged across test and retest
scans, and the mean and SD was calculated across the 7 subjects. Retest BPND by 2T and MA1 of 3 subjects were
estimated from VT that used scaled input function from the test study of each subject by the injection dose. Blood
data do not affect the calculation of BPND for equilibrium data.
BPND: binding potential, ROI: region of interest, 2T: two-tissue compartment model, MA1: multilinear analysis 1, t*:
starting time, EQ: equilibrium analysis using data from 90 to 120 min p.i.
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Test-retest reproducibility of [18F]FPEB
Online Resource Table S2. Test-retest variability (TRV) results of BPND by different analysis methods using cerebellar white matter (CWM) as a
reference region.
Mean TRV (%)
SD of TRV (%)
Mean aTRV (%)
ICC
ROI
2T
MA1
EQ
2T
MA1
EQ
2T
MA1
EQ
2T
MA1
EQ
anterior cingulate
1
0
-2
11
11
16
7
8
11
0.86
0.86
0.83
posterior cingulate
2
3
1
19
14
20
14
11
15
0.94
0.96
0.93
frontal
1
2
0
14
12
17
9
8
10
0.85
0.87
0.84
temporal
-1
3
-1
18
11
18
12
7
12
0.81
0.88
0.85
parietal
0
4
0
18
12
19
14
10
13
0.88
0.92
0.88
occipital
3
4
1
17
14
21
12
10
15
0.89
0.91
0.87
hippocampus
1
1
-4
14
13
17
9
9
13
0.83
0.85
0.85
caudate nucleus
4
4
-1
11
9
15
10
8
11
0.87
0.90
0.88
putamen
0
2
-1
11
9
14
8
6
9
0.84
0.87
0.83
pallidum
4
4
2
10
12
18
7
10
11
0.88
0.85
0.77
thalamus
1
2
0
12
11
17
8
7
10
0.87
0.89
0.84
Mean
1
3
-1
14
12
18
10
8
12
0.85
0.88
0.87
n=7
For 2T and MA1, values of 3 subjects were calculated using the retest BPND estimated from VT that used scaled input function from the test study of each subject
by the injection dose.
TRV: test-retest variability, aTRV: absolute test-retest variability, BPND: binding potential, ROI: region of interest, SD: standard deviation, 2T: two-tissue
compartment model, MA1: multilinear analysis 1 with t =30 min, EQ: equilibrium analysis using data from 90 to 120 min post-injection.
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Test-retest reproducibility of [18F]FPEB
Online Resource Table S3. Test-retest variability (TRV) results of BPND by different analysis methods using cerebellar grey matter (CGM) as a
reference region.
Mean TRV (%)
SD of TRV (%)
Mean aTRV (%)
ICC
ROI
2T
MA1
EQ
2T
MA1
EQ
2T
MA1
EQ
2T
MA1
EQ
anterior cingulate
1
-1
-3
9
11
6
8
9
5
0.92
0.89
0.95
posterior cingulate
5
3
0
23
14
10
15
11
7
0.97
0.99
0.99
frontal
1
2
-1
10
11
8
7
9
6
0.89
0.87
0.93
temporal
-1
3
-2
13
6
5
8
5
5
0.83
0.94
0.97
parietal
0
3
-1
9
4
6
7
4
4
0.95
0.98
0.98
occipital
3
4
0
8
8
9
7
7
7
0.95
0.95
0.96
hippocampus
0
0
-7
10
10
7
9
9
7
0.94
0.94
0.97
caudate nucleus
4
3
-2
3
3
4
5
4
4
0.98
0.98
0.99
putamen
-1
2
-2
7
8
4
6
7
4
0.96
0.95
0.98
pallidum
8
8
4
29
31
22
24
26
19
0.86
0.85
0.88
thalamus
1
1
-2
10
10
8
8
8
7
0.96
0.95
0.97
Mean
2
3
-2
12
11
8
9
9
7
0.93
0.94
0.96
n=7
For 2T and MA1, values of 3 subjects were calculated using the retest BPND estimated from VT that used scaled input function from the test study of each subject
by the injection dose.
TRV: test-retest variability, aTRV: absolute test-retest variability, BPND: binding potential, ROI: region of interest, SD: standard deviation, 2T: two-tissue
compartment model, MA1: multilinear analysis 1 with t*=30 min, EQ: equilibrium analysis using data from 90 to 120 min post-injection.
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Test-retest reproducibility of [18F]FPEB
FIGURES
Online Resource Fig. S1 Comparison of BPND by different analyses methods. Each point represents
regional BPND of each subject (11 ROIs, 14 studies of 7 subjects). 2T: two-tissue compartment model,
MA1: multilinear analysis 1, t*: starting time, EQ90-120 min: equilibrium analysis using data from 90 to 120
min p.i. BPND values were calculated using cerebellar white matter (CWM) as a reference region.
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Test-retest reproducibility of [18F]FPEB
Online Resource Fig. S2 BPND estimation by equilibrium approach using an earlier and shorter time
window. Each point represents BPND of each ROI of each subject (11 ROIs, 14 studies of 7 subjects,
cerebellar white matter (CWM) was used as a reference region.).
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