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Wien Center for Alzheimers Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA
b
Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA
c
Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA
d
Johnnie B. Byrd, Sr. Alzheimers Center & Research Institute, University of South Florida, Tampa, FL, USA
e
Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA
f
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA
Abstract
Background: The segmentation of brain structures on magnetic resonance imaging scans for
calculating regional brain volumes, using automated anatomic labeling, requires the use of both
brain atlases and templates (template sets). This study aims to improve the accuracy of volumetric
analysis of hippocampus (HP) and amygdala (AMG) in the assessment of early Alzheimers
disease (AD) by developing template sets that correspond more closely to the brains of elderly
individuals.
Methods: Total intracranial volume and HP and AMG volumes were calculated for elderly subjects
with no cognitive impairment (n 5 103), with amnestic mild cognitive impairment (n 5 68), or with
probable AD (n 5 46) using the following: (1) a template set consisting of a standard atlas (atlas S),
drawn on a young adult male brain, and the widely used Montreal Neurological Institute template
(MNI template set); (2) a template set (template S set) in which the template is based on smoothing
the image from which atlas S is derived; and (3) a new template set (template E set) in which the template is based on an atlas (atlas E) created from the brain of an elderly individual.
Results: Correspondence to HP and AMG volumes derived from manual segmentation was highest
with automated segmentation by template E set, intermediate with template S set, and lowest with the
MNI template set. The areas under the receiver operating curve for distinguishing elderly subjects
with no cognitive impairment from elderly subjects with amnestic mild cognitive impairment or probable AD and the correlations between HP and AMG volumes and cognitive and functional scores
were highest for template E set, intermediate for template S set, and lowest for the MNI template set.
Conclusions: The accuracy of automated anatomic labeling and the diagnostic value of the derived
volumes are improved with template sets based on brain atlases closely resembling the anatomy of the
to-be-segmented brain magnetic resonance imaging scans.
! 2012 The Alzheimers Association. All rights reserved.
Keywords:
Volumetric segmentation; Magnetic resonance imaging; Hippocampus; Amygdala; Alzheimers disease; Mild
cognitive impairment
1. Introduction
1552-5260/$ - see front matter ! 2012 The Alzheimers Association. All rights reserved.
doi:10.1016/j.jalz.2011.07.002
400
401
Table 1
Demographic variables of diagnostic groups (N 5 217)
Diagnostic group
Variable
Age, mean (SD)
Sex (% female)
MMSE score, mean (SD)
CDR-sb, mean (SD)
NCI (n 5 103)
70.8* (5.3)
75.7%
29.1* (1.0)
0.60* (0.57)
aMCI (n 5 68)
y
76.8 (5.8)
51.4%
26.2y (2.2)
2.1y (1.18)
AD (n 5 46)
y
79.1 (7.1)
58.7%
22.3z (3.3)
5.3z (2.63)
F value or c2
P value
39.75
10.8 (c2)
176.85
110.02
,.001
,.001
,.001
,.001
Abbreviations: NCI, no cognitive impairment; aMCI, amnestic mild cognitive; AD, Alzheimers disease; MMSE, Mini-Mental State Examination; CDR-sb,
Clinical Dementia Rating Scale-sum of boxes.
NOTE. Means with different superscript symbols (*,y,z) are statistically significant at P , .05 by the post hoc Scheff!e procedure.
402
Fig. 1. An 89-year-old male subjects magnetic resonance imaging scan was randomly selected to assess the correspondence of the manually delineated hippocampus and amygdala volumes to automated segmentation using MNI template set, template S set, and template E set on the same regions. The automated
segments were superimposed on the subjects magnetic resonance imaging scan. Hippocampus is in red, and amygdala is in blue. Visually, the automated delineation of the hippocampus and amygdala using template S set and template E set was better than MNI template set.
X jAi XGi j
jAi WGi j
FP5
X 2jAi XG~i j
jAi j1jGi j
FN5
X 2jA~i XGi j
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jVa 2Vg j
Vg
403
Table 2
Segmentation quality indices for the three template sets
Template
ROI
FP
FN
VS
Left HP
Right HP
Left AMG
Right AMG
Left HP
Right HP
Left AMG
Right AMG
Left HP
Right HP
Left AMG
Right AMG
0.51
0.35
0.61
0.54
0.77
0.73
0.84
0.81
0.80
0.73
0.93
0.93
0.42
0.54
0.24
0.42
0.20
0.22
0.11
0.13
0.10
0.27
0.10
0.10
0.56
0.75
0.53
0.49
0.25
0.32
0.20
0.25
0.19
0.27
0.04
0.04
0.13
0.19
0.25
0.06
0.05
0.10
0.09
0.11
0.02
0.01
0.06
0.06
Template S set
Template E set
Abbreviations: ROI, region of interest; HP, hippocampus; AMG, amygdala; J, Jaccard similarity index; FP, false-positive ratio; FN, falsenegative ratio; VS, volume similarity index coefficient.
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Table 3
Normalized HP and AMG volumes by diagnostic groups
Template set
ROI
NCI (n 5 103)
aMCI (n 5 68)
AD (n 5 46)
F value
(df 5 2,214)
1.995* (0.26)
1.834* (0.28)
0.646* (0.06)
0.758 (0.08)
2.602* (0.24)
2.464* (0.29)
0.795* (0.06)
0.816* (0.06)
3.025* (0.29)
2.828* (0.38)
0.972* (0.07)
0.996* (0.09)
1.753y (0.26)
1.577y (0.32)
0.606y (0.08)
0.729 (0.07)
2.308y (0.28)
2.146y (0.38)
0.749y (0.07)
0.768y (0.07)
2.621y (0.33)
2.411y (0.37)
0.917y (0.08))
0.918y (0.08)
1.520z (0.33)
1.430y (0.39)
0.565z (0.1)
0.719 (0.06)
2.056z (0.42)
1.916z (0.45)
0.685z (0.10)
0.746y (0.10)
2.291z (0.47)
2.153z (0.50)
0.823z (0.11)
0.871z (0.11)
49.9
29.4
20.1
3.8
57.9
41.6
38.4
19.0
77.1
50.0
51.8
32.7
Template S set
Template E set
Neuroquant
Brain region
NCI (n 5 21)
aMCI (n 5 26)
AD (n 5 25)
F value
(df 5 2,69)
2.388* (0.26)
2.537* (0.36)
1.077* (0.10)
1.088* (0.19)
2.139y (0.24)
2.163y (0.31)
0.913y (0.15)
0.872y (0.18)
1.866z (0.34)
1.911y (0.46)
0.772z (0.17)
0.836y (0.22)
19.2
15.1
23.2
11.0
NOTE. HP and AMG volumes and SD are expressed as 1/000 of intracranial volume. All F test statistics are significant at P ,.001, except for AMG volume
right mean of the MNI template (P 5.02) set. Means with different superscript symbols (*,y,z) are significantly different from each other at P ,.05 by the Scheff!e
procedure.
volumes obtained using template E and S sets were significantly greater than those obtained using the MNI template
set. Correlations between template S and E sets were not different from each other.
4. Discussion
This study demonstrates that replacing the MNI template
set, which consists of a brain atlas (atlas S) and a template (the
MNI template), with template S set, which consists of atlas S
and a template derived from atlas S, improved the accuracy of
anatomical segmentation of the HP and AMG, as reflected in
measures of correspondence between manual and automated
Table 4
aROC values among diagnostic groups using three different templates sets
Comparison groups
and region
aMCI versus NCI
Left HP
Right HP
Left AMG
Right AMG
AD versus NCI
Left HP
Right HP
Left AMG
Right AMG
Template
S set
Template
E set
0.75* (0.04)
0.73* (0.04)
0.64* (0.05)
0.60* (0.05)
0.80* (0.04)
0.75* (0.04)
0.70* (0.04)
0.71y (0.04)
0.83y (0.03)
0.80y (0.04)
0.70* (0.04)
0.75z (0.04)
0.86*,y (0.04)
0.80* (0.04)
0.78* (0.05)
0.63* (0.06)
0.86* (0.04)
0.85y (0.04)
0.85*,y (0.04)
0.75y (0.04)
0.90y (0.03)
0.87y (0.03)
0.90y (0.03)
0.82z (0.04)
20.484
20.424
20.275
20.091
0.390
0.308
0.319
0.126
20.519
20.517**
20.424***
20.382**
0.455*
0.376*
0.414*
0.322**
20.545*
20.524**
20.434***
20.421**
0.462***
0.388***
0.437***
0.384**
NOTE. Correlation coefficients for template S and template E sets are significantly different from those for the MNI template at the following significance levels:
*P , .05.
**P , .001.
***P , .01.
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