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AAN –Toronto, April 11, 2010
Development of a harmonized
protocol for hippocampal tracing
An EADC-ADNI joint effort
METHODS
METHODS
Operationalization of protocols’ differences and
extraction of tracing units
Quantification of tracing units’ features
Harmonized protocol
OPERATIONALIZATION
Selection of segmentation protocols
Selection criteria
i) Being based on 3D T1 MRI with field strength
greater than 1 Tesla
ii) Providing explicit description of landmarks for
tracing of hippocampal borders
iii) Being validated on AD/MCI samples, or being widely
adopted in the literature about AD.
OPERATIONALIZATION
Protocols’ features extraction
Areas explicitly
included
Areas explicitly
excluded
Andreas-Retzius
CA regions, dentate
gyrus (ARG), the part
gyrus, subiculum,
of the FG that is
alveus, fimbria, part of
adjacent to ARG, crus
the fasciolar gyrus (FG)
of fornix
Most anterior slice
Most posterior slice
slice w here one of the
follow ing is visible: alveus,
temporal horn of lateral
ventricle (uncal recess) or
amygdala
slice w here an ovoid mass of
gray matter started to appear
inferomedially to the trigone of the
lateral ventricle
Plane of tracing: AC-PC line;
BOUNDARIES
Normalization to the Talairach space
HEAD
Lateral border
temporal horn of
lateral ventricle
(uncal recess)
Inferior border
Medial border
Superior border
CSF of ambient cistern
temporal horn of lateral ventricle
(uncal recess) and alveus
Tracing start from the tail of
hippocampus to the hippocampal head
uncal cleft (if visible)
In the following slices, you can find the
BODY
temporal horn of
lateral ventricle
(uncal recess)
White matter of the
parahippocampal
gyrus
CSF of ambient cistern
superior excess of the
quadrigeminal cistern
TAIL
hippocampal tracing on consecutive
Discrimination of
HT from FG and
crus of fornix
using arbitrary
borders
adjacent w hite matter
atrium of lateral ventricle
Discrimination of HT from ARG
using arbitrary borders
coronal slices (1.5T) of the control
subject and AD patient according to
Pruessner's criteria
OPERATIONALIZATION
Prototypical tracings
Tracings carried out on a control and an
AD subject from the ADNI dataset
Tracings sent to the Authors for correction
or approval
CTRL
Most posterior slice : slice where
The fornix can be excluded by a
an ovoid mass of gray matter (1)
started to appear inferomedially of horizontal line (in fuchsia) from
the superior border of the
the atrium of lateral ventricle (2)
quadrigeminal cistern (3) to the
lateral ventricle (2).
Part of gyrus fasciolaris (7) and of
Sagittal Andreas-Retzius gyrus (8) can be
excluded by a vertical line (in red)
view
from the medial end of the lateral
ventricle (2) down to the
parahippocampal gyrus (4).
2= Atrium of lateral ventricle
4= Parahippocampal gyrus
5= Gyrus dentatus
6= Cornu Ammonis
7= Gyrus fasciolaris
8= Gyrus of Andreas-Retzius
9= Isthmus
AD
Most posterior slice : slice where
In AD subjects the cerebral structures are atrophic, lateral
an ovoid mass of gray matter (1)
started to appear inferomedially of ventricle (2) and ambient cistern (3) result enlarged. Therefore,
the lines used to exclude the gyrus fasciolaris, the Andreasthe atrium of lateral ventricle (2)
Retzius gyrus and the fornix do not intersect the hippocampal
tail. That being so, is there another way to exclude the gyrus
fasciolaris, the Andreas-Retzius gyrus and the fornix in these
Sagittal
subjects?
view
2= Atrium of lateral ventricle
4= Parahippocampal gyrus
5= Gyrus dentatus
6= Cornu Ammonis
7= Gyrus fasciolaris
8= Gyrus of Andreas Retzius
9= Isthmus
OPERATIONALIZATION
Authors’ check
For each protocol:
features extraction, tracing and author’s certification
CTRL
Areas explicitly
included
Areas explicitly
excluded
Andreas-Retzius
CA regions, dentate
gyrus (ARG), the part
gyrus, subiculum,
of the FG that is
alveus, fimbria, part of
adjacent to ARG, crus
the fasciolar gyrus (FG)
of fornix
Most anterior slice
Most posterior slice
slice w here one of the
follow ing is visible: alveus,
temporal horn of lateral
ventricle (uncal recess) or
amygdala
slice w here an ovoid mass of
gray matter started to appear
inferomedially to the trigone of the
lateral ventricle
Inferior border
Medial border
Superior border
temporal horn of
lateral ventricle
(uncal recess)
uncal cleft (if visible)
CSF of ambient cistern
temporal horn of lateral ventricle
(uncal recess) and alveus
BODY
AD
temporal horn of
lateral ventricle
(uncal recess)
White matter of the
parahippocampal
gyrus
CSF of ambient cistern
superior excess of the
quadrigeminal cistern
TAIL
HEAD
BOUNDARIES
Lateral border
Discrimination of
HT from FG and
crus of fornix
using arbitrary
borders
adjacent w hite matter
atrium of lateral ventricle
Discrimination of HT from ARG
using arbitrary borders
X 10
OPERATIONALIZATION
Extraction of similarities and differences
Harmonized language
Reduction of redundancy
Tracing units and subunits
Plane of tracing
Axis of
hippocampus
[B,C,J,L,S]
AC-PC line [H,K,M,Pa,Pr]
Most posterior
slice
Areas explicitly included
Areas explicitly
excluded
portion of subiculum, CA
fields
choroid plexis of inferior
horn, amygdala
Where inferior and
superior colliculi
are jointly
visualized [B]
Most posterior slice
Most anterior slice
Where crus of
fornix is visible in
full profile [C,K,L]
Where the crura of the fornices
are seen in full profile on both
sides [J,S]
Upper border of
alveus/fimbria
[C,J,L,M,Pr]
Horizontal line from the
superior border of the
quadrigeminal cistern to the
lateral ventricle (tail) [Pr]
45° line connecting
the most inferior
part of the
subiculum medially
to the cistern (head
and body) [Pr]
Oblique line with same
inclination of parahippocampal
WM, connecting the inferior
part of the subiculum to the
quadrigeminal cistern [K,L,M¥]
slice in w hich the fornix
level at w hich the alveus
distinguishes the amygdala appeared as a solid w hite line
through the collateral trigone
from hippocampus
Where gray matter
is visible
inferomedially to
the trigone of the
lateral ventricle
[H,M•,Pa•,Pr]
Superior border
Inferior border
Medial border
Superior border
HEAD
inferior horn of the
lateral ventricle
w hite matter joining the
parahippocampal gyrus
angular bundle
inferior horn of the lateral
ventricle
BODY
Areas explicitly
included
Lateral border
same as head
same as head
same as head
same as head
TAIL
BOUNDARIES
same as head
Areas explicitly
excluded
Most anterior slice
same as head
Separation
subiculum/enthor
inal cortex
Most posterior slice
same as head
same as head
Andreas-Retzius
slice w here one of the
CA regions, dentate
slice w here an ovoid mass of
gyrus (ARG), the part
follow ing is visible: alveus,
gyrus, subiculum,
gray matter
started to appear
Areas explicitly
of the FG that Plane
is tracing temporal horn
lateralincluded
Areasof
explicitly
anterior slice
alveus, fimbria, part of
inferomediallyexcluded
to the trigone Most
of the
adjacent to ARG, crus
ventricle (uncal recess) or
the fasciolar gyrus (FG)
lateral ventricle
the separation of amygdala
of fornix
amygdala
axial + coronal +
sagittal
Lower border of
alveus/fimbria
[B,H,K,Pa,S]
Cornu Ammonis, subiculum, vertical digitation
alveus and fimbria
BOUNDARIES
Most posterior slice
coronal section in w hich the
and hippocampal head w as
hippocampus first appeared
facilitated by sagittal and adjacent to the trigone of lateral
transverse view s
venticle
Inferior border
HEAD
uncal cleft (if visible)
BODY
Medial border
Medial border
temporal horn of
lateral ventricle
(uncal recess)
White matter of the
parahippocampal
gyrus
Discrimination of
HT from FG and
crus of fornix
using arbitrary
borders
adjacent w hite matter
BODY
HEAD
Lateral border
temporal horn of
lateral ventricle
(uncal recess)
TAIL
BOUDARIES
Gyrus ambiens
CSF of ambient cistern
Inferior border
Superior border
identified by the
contrast of the WM
WM of parahippocampal
identified by the contrast of the
WM or CSF
identified by the
contrast of the WM
or CSF
WM of parahippocampal
gyrus
The medial border of the HC w as continued w ith a
straight horizontal line (marking the inferior border
of CA and subiculum) across the cortex of the
PHG. The cortex below this line w as considered
the PHG, and the cortex above this line w as
included as a part of the HC
CSF of ambient
cistern
TAIL
Superior
border
Lateral border
gyrus (PHG)
temporal horn orofCSF
lateral ventricle
(uncal recess) and alveus
The medial border of the HC w as continued w ith a
straight horizontal line (marking the inferior border
of CA and subiculum) across the cortex of the
PHG. The cortex below this line w as considered
the PHG, and the cortex above this line w as
included as a part of the HC
atrium of lateral ventricle
identified by the contrast of the
WM or CSF
superior excess of the
quadrigeminal cistern
identified by the
contrast of the WM
or CSF
WM of parahippocampal
gyrus
Discrimination of HT from ARG
using arbitrary borders
identified by the contrast of the
WM or CSF, and Thalamus and
caudate nucleus
vertical line from
the CA to the WM
of the
parahippocampal
gyrus [C]
Orizontal line from
the highest medial
point of the
parahippocampal
WM to the cistern
[B,H,J¥]
Line outlining
the contour of
white matter of
parahippocamp
al gyrus [Pa,S]
OPERATIONALIZATION
Extraction of similarities and differences
Areas explicitly included
Areas explicitly
excluded
portion of subiculum, CA
fields
choroid plexis of inferior
horn, amygdala
Most anterior slice
Most posterior slice
slice in w hich the fornix
level at w hich the alveus
distinguishes the amygdala appeared as a solid w hite line
through the collateral trigone
from hippocampus
Inferior border
Medial border
Superior border
HEAD
inferior horn of the
lateral ventricle
w hite matter joining the
parahippocampal gyrus
angular bundle
inferior horn of the lateral
ventricle
BODY
BOUNDARIES
Lateral border
same as head
same as head
same as head
same as head
same as head
Areas explicitly
excluded
same as head
Most posterior slice
Most anterior slice
same as head
Andreas-Retzius
CA regions, dentate
gyrus (ARG), the part
gyrus, subiculum,
of the FG that is
alveus, fimbria, part of
adjacent to ARG, crus
the fasciolar gyrus (FG)
of fornix
same as head
slice w here one of the
follow ing is visible: alveus,
temporal horn of lateral
ventricle (uncal recess) or
amygdala
slice w here an ovoid mass of
gray matter started to appear
inferomedially to the trigone of the
lateral ventricle
Inferior border
Medial border
Superior border
HEAD
temporal horn of
lateral ventricle
(uncal recess)
uncal cleft (if visible)
CSF of ambient cistern
temporal horn of lateral ventricle
(uncal recess) and alveus
BODY
BOUNDARIES
Lateral border
temporal horn of
lateral ventricle
(uncal recess)
White matter of the
parahippocampal
gyrus
CSF of ambient cistern
superior excess of the
quadrigeminal cistern
TAIL
TAIL
Areas explicitly
included
Discrimination of
HT from FG and
crus of fornix
using arbitrary
borders
adjacent w hite matter
atrium of lateral ventricle
Discrimination of HT from ARG
using arbitrary borders
Plane of tracing
Axis of hippocampus
[B,C,J,L,S]
AC-PC line [H,K,M,Pa,Pr]
Where inferior and
superior colliculi are
jointly visualized [B]
Where crus of fornix is visible
in full profile [C,K,L]
Lower border of
alveus/fimbria
[B,H,K,Pa,S]
Upper border of alveus/fimbria
[C,J,L,M,Pr]
45° line connecting the
most inferior part of the
subiculum medially to
the cistern (head and
body) [Pr]
Oblique line with same
inclination of parahippocampal
WM, connecting the inferior
part of the subiculum to the
quadrigeminal cistern
[K,L,M¥]
Most posterior slice
Where the crura of the fornices
are seen in full profile on both
sides [J•,S]
Where gray matter is visible
inferomedially to the trigone
of the lateral ventricle
[H,M•,Pa•,Pr]
Superior border
Horizontal line from the
superior border of the
quadrigeminal cistern to the
lateral ventricle (tail) [Pr]
Separation
subiculum/enthorinal
cortex
vertical line from the CA
to the WM of the
parahippocampal gyrus
[C]
Orizontal line from the highest
medial point of the
parahippocampal WM to the
cistern [B,H,J¥]
Line outlining the contour of
white matter of
parahippocampal gyrus
[Pa,S]
METHODS
Operationalization of protocols’ differences
Quantification of tracing units’ features
Harmonized protocol
QUANTIFICATION OF TRACING UNITS’ FEATURES
Contribution to hippo volume in
control and AD
Effect on re-test variability
Contribution to differences between
AD and controls
METHODS
Operationalization of protocols’ differences
Quantification of tracing units’ features
Harmonized protocol
HARMONIZED PROTOCOL
Participants to a Delphi panel based on:
expertise in hippocampal anatomy
manual tracing scientific production
Assisted decisions based on:
Low variability, highly informative..
..included in harmonized protocol
High variability, little informative..
..excluded from harmonized prot
HARMONIZED PROTOCOL
Validation & implementation
Validation with neuropathological data
Comparison with currently used protocols
Public tracings and probability maps
Standard environment for tracing, learning, and
certification