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Figure Legends
Figure 1 Definition of the neuromelanin (NM)-positive region in the substantia
nigra (SN) and reference region in the rostral pons. Top left: A group-averaged NM
map was delineated in the SN by manually outlining the hyperintense area on the
NM-magnetic resonance imaging (MRI) template generated from healthy control
participants (orange). NM accumulates in dopamine neurons which are rich in the SN
pars compacta, although boundaries between the SN pars compacta and SN pars
reticulata are difficult to identify with MRI. Top right: The reference region was set in
the rostral pontine area on the NM-MRI template (yellow). The reference region on the
template was transformed on an individual NM-MRI to normalize the signal intensity
by removing inter-participant variability. Bottom left: The group-averaged NM map on
the template was projected on the individual NM-MRI acquired perpendicular to the
cerebral aqueduct, and hyperintense voxels having above 50th percentile value in the
projected NM map were selected. For display purposes, representative healthy control
participant data are represented (green). The mean signal intensity of the selected voxels
was computed as the contrast ratio (CR) of SN. Bottom right: Hyperintense voxels
having suprathreshold intensity, that is, 1.05, in the registered NM map were identified,
and total volumes were calculated as the volume of NM-positive regions.
Representative healthy control participant data are displayed (magenta).
Figure 2 Correlation between MDS-UPDRS Part III score and the striatal uptake
ratio (A) and the contrast ratio (CR) (B) and volume (C) of the neuromelanin
(NM)-positive region in the substantia nigra (SN) at early- (disease duration ≤8
years: blue) and advanced-stage (disease duration >8 years: red) of Parkinson’s
disease. The striatal uptake ratio, substantia nigra CR and volume were adjusted for the
effects of age and sex by linear regression. Regression lines are presented for each stage
(solid line: statistically significant; dotted line: nonsignificant). The MDS-UPDRS Part
III score was evaluated during the drug-off state.
Figure 3 Correlation between MDS-UPDRS Part III score and the striatal uptake
ratio (A) and the contrast ratio (CR) (B) and volume (C) of the neuromelanin
(NM)-positive region in the substantia nigra (SN) in Parkinson’s disease (PD)
patients without (gray cross) and with motor fluctuation (black dot). The striatal
uptake ratio, substantia nigra CR and volume were adjusted for the effects of age and
sex by linear regression. Regression lines are presented for each group (PD without
motor fluctuation: gray; PD with motor fluctuation: black; solid line: statistically
significant; dotted line: nonsignificant). The MDS-UPDRS Part III score was evaluated
during the drug-off state.
Figure 4 Correlation between the striatal uptake ratio and the contrast ratio (CR)
(A) and volume (B) of the neuromelanin (NM)-positive region in the substantia
nigra (SN) at early- (disease duration ≤8 years: blue) and advanced-stage (disease
duration >8 years: red) of patients with Parkinson’s disease. Regression lines are
presented for each stage (solid line: statistically significant; dotted line: nonsignificant).
Figure 5 Correlation between the striatal uptake ratio and the contrast ratio (CR)
(A) and volume (B) of the neuromelanin (NM)-positive region in the substantia
nigra (SN) in Parkinson’s disease (PD) patients without (gray cross) and with
motor fluctuation (black dot). Regression lines are presented for each group (PD
without motor fluctuation: gray; PD with motor fluctuation: black; solid line:
statistically significant; dotted line: nonsignificant).
Table 1. Clinical characteristics of patients with early (disease duration ≤ 8 years) and advanced
Parkinson’s disease (> 8 years)
≤8 years (n=45)
>8 years (n=48)
P value
Age
63.3 ± 10.9
64.1 ± 7.6
0.71a
Female:Male
22:23
28:20
0.36b
Disease duration
4.7 ± 2.3
11.5 ± 3.2
<0.0001a
LEDD
407.8 ± 362.7
807.2 ± 376.1
<0.0001a
Hoehn and Yahr (off)
2.3 ± 0.9
3.3 ± 1.2
<0.0001a
Hoehn and Yahr (on)
1.9 ± 0.5
2.1 ± 0.5
<0.01a
MDS-UPDRS Part III score (off)
34.8 ± 12.1
46.5 ± 16.6
<0.001a
MDS-UPDRS Part III score (on)
21.3 ± 10.2
20.8 ± 10.8
0.81a
Independent t-test and bPearson's chi-square test used for both groups. On = drug-on state; off = drug-off
state. LEDD = levodopa daily equivalent dose
Table 2. Clinical characteristics of patients with early (disease duration ≤10 years) and advanced
Parkinson’s disease (>10 years)
≤10 years (n=66)
>10 years (n=27)
P value
Age
63.6±9.9
63.9±7.8
0.89a
Female: Male
34:32
16:11
0.50b
Disease duration
6.0 ± 2.7
13.7 ± 2.7
<0.0001a
LEDD
482.5 ± 361.9
935.2 ± 377.2
<0.0001a
Hoehn and Yahr (off)
2.4 ± 0.9
3.9 ± 1.1
<0.0001a
Hoehn and Yahr (on)
1.9 ± 0.5
2.2 ± 0.6
< 0.05a
MDS-UPDRS Part III score (off)
38.1 ± 13.6
47.4 ± 18.4
< 0.01a
MDS-UPDRS Part III score (on)
21.3 ± 10.5
20.3 ± 10.7
0.65a
Independent t-test and bPearson's chi-square test for the two groups. On=drug-on state; off=drug-off state.
LEDD = levodopa daily equivalent dose.
Table 3. Clinical characteristics of Parkinson’s disease patients without and with motor fluctuation
Without motor fluctuation With motor fluctuation
P value
(n=31)
(n = 62)
Age
64.9 ± 12.0
63.1 ± 7.6
0.37a
Female:Male
17:14
33:29
0.88b
Disease duration
4.3 ± 3.1
10.2 ± 3.7
< 0.0001a
LEDD
237.4 ± 233.3
802.2 ± 360.3
< 0.0001a
Hoehn and Yahr (off)
2.0 ± 0.7
3.2 ± 1.1
< 0.0001a
Hoehn and Yahr (on)
1.8 ± 0.5
2.1 ± 0.5
< 0.01a
MDS-UPDRS Part III score (off) 33.0 ± 12.4
44.7 ± 15.7
< 0.001a
MDS-UPDRS Part III score (on)
20.3 ± 10.1
0.37a
22.4 ± 11.3
Independent t-test and bPearson's chi-square test for the two groups. On = drug-on state; off = drug-off
state. LEDD = levodopa daily equivalent dose.
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