Vessel-based

registration
with
application
to
nodule
detection

in
thoracic
CT
scans

Changhua
Wua
and
Gady
Agamb

a
Department
of
Science
and
Mathematics,
Kettering
University,
Flint,
MI
48504
b
Department
of
Computer
Science,
Illinois
Institute
of
Technology,
Chicago,
IL
60616

ABSTRACT

Volume
registration
is
fundamental
to
multiple
medical
imaging
algorithms.
Speci
cally,
non-rigid
registration
of
thoracic
CT
scans
taken
at
dierent
time
instances
can
be
used
to
detect
new
nodules
more
reliably
and
assess
the
growth
rate
of
existing
nodules.
Voxel-based
registration
techniques
are
generally
sensitive
to
intensity
variation
and
structural
dierences,
which
are
common
in
CT
scans
due
to
partial
volume
eects
and
naturally
occurring
motion
and
deformations.
The
approach
we
propose
in
this
paper
is
based
on
vessel
tree
extraction
which
is
then
used
to
infer
the
complete
volume
registration.
Vessels
form
unique
features
with
good
localization.
Using
extracted
vessel
trees,
a
minimization
process
is
used
to
estimate
the
motion
vectors
at
vessels.
Accurate
motion
vectors
are
obtained
at
vessel
junctions
whereas
vessel
segments
support
only
normal
component
estimation.
The
obtained
motion
vectors
are
then
interpolated
to
produce
a
dense
motion
eld
using
thin
plate
splines.
The
proposed
approach
is
evaluated
on
both
real
and
synthetically
deformed
volumes.
The
obtained
results
are
compared
to
several
standard
registration
techniques.
It
is
shown
that
by
using
vessel
structure,
the
proposed
approach
results
in
improved
performance.

1.
INTRODUCTION
Successful
registration
is
fundamental
to
the
fusion
of
medical
images
and
the
diagnosis
of
abnormal
structures
from
temporal
images.
Computerized
volumetric
warping
and
registration
of
3D
lung
images
can
provide
obj
ective,
accurate,
and
reproducible
measures
to
the
understanding
of
the
lung
structure
and
function.
It
is
also
invaluable
to
the
assessment
of
the
presence
of
diseases
and
their
response
to
therapies.
In
the
automated
computer
diagnosis
of
nodules,
the
dierence
between
temporal
CT
scans
after
registration
can
be
used
to
track
the
development
of
existing
nodules
and
detect
new
ones.1,
2
The
change
in
size
and
intensity
can
be
used
to
tell
whether
a
nodule
is
malignant
or
benign.3
Registration
can
be
used
to
estimate
regional
lung
expansion,4
breathing
motion,5,
6
and
structure-function
relationships.7,
8
It
can
also
be
used
to
reduce
the
false
positive
in
nodule
detection.9,
10

However
only
limited
work
that
targets
the
accurate
registration
of
lung
volumes
has
been
done.
Some
work2
used
the
iterative
closest
point
(ICP)
to
register
the
contours
of
lung
volumes.
Zhang
Li11
developed
a
3D
surface-
based
registration
technique
to
register
pulmonary
CT
volumes.
The
registration
includes
a
global
transformation
and
a
local
elastic
transformation
by
subdividing
the
image
and
atlas
volume
into
sub-images
called
cubes.
The
displacement
vectors
of
each
cube
are
processed
using
Burr's
dynamic
model
to
give
a
smoothed
deformation
vector
for
each
voxel
in
the
image.
However,
this
approach
is
entirely
dependent
on
the
intensity
information
and
makes
no
use
of
a
priori
knowledge
of
the
lung
structure
such
as
the
vessel
network.
Some
researchers
try
to
estimate
the
transformation
eld
by
nding
matches
of
the
junctions
of
vessels
and
airways
in
the
lung
volume.
Fan
Li12,
13
proposed
an
interpolation
method
for
obtaining
dense
transformation
eld
from
sparse
displacement
vectors
obtained
by
tracking
the
bronchial
points
of
airways.
The
dense
transformation
eld
is
obtained
by
minimizing
an
object
function
based
on
a
model
of
continuum
mechanics
and
anisotropic
smoothness
constraints.
This
approach
assumes
that
the
intensity
of
a
point
in
the
lung
does
not
change
in
all
scans.
However
this
is
not
always
true,
especially
in
thick
CT
scans
due
to
the
partial
volume
eect.
Prado14
proposed
a
sequential
polynomial
registration
scheme
to
interactively
register
lung
volumes.
The
coecients
of
the
polynomial
function
are
updated
by
adding
control
points
manually.
Due
to
the
limited
degree,
the
polynomial
function
may
not
be
capable
of
accurately
describing
the
non-rigid
deformation
between
lung
volumes.
Moreover,
the
manual

E-mail:
agam@iit.edu,
cwu@kettering.edu
interaction
may
introduce
error
in
the
position
of
control
points
and
also
reduces
the
eciency.
Shikata15
proposed
a
lung
registration
method
by
matching
bifurcation
points
from
a
reconstructed
vessel-tree.
However,
it
only
estimated
a
rigid
transformation
eld
while
the
real
transformation
between
lung
volumes
is
non-rigid.
Finally,
Baojun
Li7
proposed
a
method
to
combine
the
junctions
of
airway
with
intensity
consistency.
In
his
method,
the
similarity
between
junctions
and
voxels
are
measured
by
a
set
of
cost
functions,
which
are
minimized
to
get
the
nal
transformation
eld.
However,
the
matching
between
junctions
is
manually
established,
which
reduces
its
eciency
and
makes
it
unsuitable
for
automated
lung
registration.
Further
more,
it
is
hard
to
avoid
local
minimum
in
the
minimization
of
the
cost
functions.

In
this
paper,
an
automatic
registration
method
based
on
the
structure
of
vessels
is
proposed.
This
paper
is
organized
as
follows.
Section
2
presents
in
detail
the
proposed
approach
for
registering
thoracic
CT
scans.
Initial
alignment,
landmark
selection,
interpolation
of
transformation
eld,
incorporation
of
smoothness
and
vessel-based
constraints
are
discussed
in
this
section.
Section
3
discusses
the
evaluation
of
the
proposed
method.
Section
4
presents
the
conclusion
and
outlines
the
future
work.

2.
THE
PROPOSED
APPROACH
Blood
vessels
are
prominent
features
in
thoracic
CT
scans.
The
network
of
vessels
covers
most
of
the
volume,
which
makes
vessels
good
landmarks
in
the
registration
of
lung
volumes.
In
this
section,
a
general
registration
algorithm
that
uses
vessel-based
landmarks
to
register
CT
volumes
is
proposed.
The
proposed
registration
algorithm
uses
both
junctions
and
vessels
to
estimate
the
non-rigid
transformation
between
volumes.
False
matching
of
junctions
are
removed
by
smoothness
constraint
using
the
curvatures
of
the
transformation
eld.
Then
the
registration
is
further
improved
by
incorporating
the
linear
vessel
segments
whose
matches
are
found
by
actively
deforming
their
center
lines
to
their
matches.
This
section
is
organized
as
follows.
Section
2.1
discusses
the
initial
alignment.
Junction
detection
is
discussed
in
section
2.2.
Section
2.3
introduces
thin-plate
splines
(TPSs),
which
are
used
in
the
interpolation
of
the
transformation
eld.
Section
2.4
discusses
the
enforcement
of
smoothness
constraints
on
the
transformation
eld.
Section
2.5
discusses
the
incorporation
of
vessel
constraints.

2.1.
Initial
alignment
At
the
beginning,
the
source
and
the
target
volumes
are
initially
aligned
through
an
ane
transformation.
This
initial
alignment
reduces
the
searching
space
in
nding
matches
for
junctions
and
vessels.
An
ane
transformation
is
composed
of
translation,
rotation,
and
scaling.
The
translation
component
is
estimated
from
the
center
of
the
volumes.
Let
the
centers
of
the
source
volume
and
the
target
volume
be
denoted
by
c
=
fcx;cy;czgT
and

c=
fc;c;cgT
respectively.
The
translation
matrices
T
and
T
.
that
move
the
centers
of
both
the
source
and

xyz
target
volumes
to
their
origins
respectively
are
given
by:

.
.

I
..cI
..c.

T
=
;T
.
=
(1)
01
01

where
I
is
an
3
×
3
identity
matrix.

The
rotation
and
scaling
components
are
estimated
from
the
principal
component
analysis
of
the
lung
volume.
Let
V
and
V
.
denote
the
sets
containing
all
the
voxels
of
the
source
and
target
volumes
respectively.
The
principal
directions
of
each
volume
can
be
obtained
by
eigenvalue
decomposition
of
the
covariance
matrices
M
and
M
0:

M
=(v
-
c).
(v
-
c);M.
=(v
-
c
0)0(v
-
c
.
)
(2)
v2Vv2V
.

Let
P
=
fp1;p2;p3}
be
the
eigenvectors
of
M
and
P
.
=
fp1;p2;p3}
be
the
eigenvectors
of
M
.
such
that
pij3

i=1

corresponds
to
pij3
i=1.
The
correspondence
between
eigenvectors
can
be
known
by
looking
for
the
pairs
of
eigenvectors
that
are
closest
to
each
other
in
direction
in
P
and
P
.
.
The
rotation
matrices
R
and
R.
that
align
the
volumes
to
the
coordinate
systems
de
ned
by
P
and
P
.
are
given
by

..1
..1

p1
p2
p3
0
ppp0

R.
123
R
=
,
=
(3)
0001
0001
Let
E
=
f1;2;3gT
and
E.
=
f.
1;2
.
;.
3gT
be
the
eigenvalues
corresponding
to
the
eigenvectors
in
P
and
P
.
.
The
scaling
matrices
S
and
S.
that
transform
both
the
source
and
target
volumes
to
a
unit
volume
are
given
by:

23..1
.
.
3..1

1
0
00
1
0
00
.
7.
.
.
0
2
00
000

6.
S.
.
2
7
S
=
,
=
(4)

.
00
3
0
5.
00
.
3
0
.
0001
0001

Using
the
matrices
above
to
normalize
the
source
volume
Is
and
the
target
volume
It,
we
get
SRT
Is
=
S0R0T
0It.
So
the
ane
transformation
matrix
Ma
that
aligns
Is
to
It
is:

..1
Ma
=(S.
R0T
0)SRT
(5)

2.2.
Landmark
selection
There
are
two
general
approaches
in
image
registration,
voxel-based
approaches
and
landmark-based
approaches.
The
voxel-based
approaches
use
the
intensity
of
all
voxels
in
the
overlapping
area.
Similarity
measures
such
as
mutual
information
and
intensity
correlation
are
widely
used
in
voxel-based
approaches.
Usually,
no
human
interaction
is
needed.
Landmark-based
approaches,
on
the
other
hand,
use
only
a
set
of
feature
points.
Comp
ared
with
voxel-based
approaches,
landmark-based
approaches
can
take
advantage
of
a
priori
knowledge
of
the
structures.
Due
to
high
uence
in
of
landmarks
on
the
accuracy
of
image
registration,
it
is
common
that
the
landmarks
are
manually
selected.
Voxel-based
approaches
treat
voxels
of
tissue
and
structures
in
the
same
way
while
landmark-based
approaches
give
higher
weight
to
structures.
Voxel-based
approaches
are
also
more
sensitive
to
noise
and
intensity
variation.

Since
vessels
in
the
CT
scans
can
be
easily
obtained
after
enhancement16,
17
and
we
care
more
about
the
accurate
registration
of
vessels
than
irrelevant
tissue,
the
proposed
approach
is
based
on
landmarks
detected
from
enhanced
vessels.
Two
criteria
are
considered
in
selecting
such
landmarks.
First,
they
should
represent
some
distinguishable
anatomical
features
that
can
be
accurately
identi
ed
and
matched.
Second,
they
should
be
spatially
distributed
as
uniformly
as
possible
to
provide
adequate
information
throughout
the
volume.
According
to
these
criteria,
junctions
of
vessels
are
ideal
candidates.
They
have
been
widely
used
in
image
registration.15,
18
After
enhancement,
vessels
can
be
segmented
by
a
simple
thresholding.
Linear
vessel
segments
can
be
obtained
by
tracing
along
vessel
directions
until
junctions
are
met.
In
the
proposed
approach,
junctions
are
detected
by
checking
the
eigenvalues
of
the
gradient
correlation
matrix.
Let
1
.
2
be
the
eigenvalues
of
the
matrix.
It
is
assumed
that
for
linear
vessel
segments,
2
is
near
to
zero
and
1
is
much
bigger
than
2,
therefore
2=1
is
very
small.
So
to
detect
junctions,
we
only
need
to
check
the
value
of
2=1.
If
it
is
larger
than
a
threshold,
then
a
junction
is
detected.
To
ensure
that
the
selected
junctions
are
uniformly
distributed
in
the
volume,
a
post-process
is
applied
to
remove
junctions
that
are
too
close
to
each
other
so
that
the
distance
between
any
two
junctions
is
above
a
minimum
distance
(30
voxels
in
the
experiments).
For
each
junction
left,
its
match
in
the
target
volume
is
searched
within
a
20×
20×
5
window.
Since
the
translation
is
usually
smaller
than
5
voxels
after
the
initial
alignment,
this
window
is
big
enough
to
nd
a
match.
The
similarity
between
junctions
is
measured
by
intensity
correlation
in
a
10
×
10
window.
To
improve
the
accuracy
of
registration,
only
those
junction
pairs
with
high
correlation
(top
50%
among
all
matching
pairs
of
junctions)
are
kept.
The
remaining
junction
pairs
are
then
used
to
generate
a
smooth
transformation
eld
through
thin-plate
spline
interpolation.

2.3.
Interpolation
of
the
transformation
eld
In
the
proposed
approach,
the
transformation
eld
is
interpolated
using
thin-plate
splines
(TPSs),
which
belong
to
a
family
of
splines
based
on
radial
basis
functions.
TPS
has
been
formulated
by
Duchon19
and
Meinguet20
for
surface
interpolation
of
scattered
data.
TPS
models
the
deformation
of
a
thin
metal
plate
under
external
forces.
The
surface
interpolated
by
TPS
passes
through
the
control
points.
Each
control
point
has
global
in
uence
on
the
shape
of
the
interpolated
surface.
In
recent
years
TPS
has
been
widely
used
in
image
registration.21{23
The
de
nition
of
TPS
is
a
linear
combination
of
n
radial
basis
functions
(s):

t(x,
y,
z)=
a1
+
a2x
+
a3y
+
a4z
+
bj(jj
-
(x,
y,
z)j)
(6)
j=1
De
ning
the
transformation
as
three
separate
thin-plate
spline
functions
T
=(t1;t2;t3)T
yields
a
mapping
between
images
in
which
the
coecients
a1,
a2,
a3
and
a4
characterize
the
ane
part
of
the
transformation
while
the
coecients
fbjgj=1:::n
characterize
the
non-ane
part
of
the
transformation.
The
n
control
points
form
a
set
of
3n
linear
equations.
To
determine
the
3(n
+
4)
coecients
uniquely,
twelve
additional
equations
are
required.
These
twelve
equations
guarantee
that
the
non-ane
coecients
fbjgj=1:::n
sum
to
zero
and
that
their
crossproducts
with
the
x,
y
and
z
coordinates
of
the
control
points
are
likewise
zero.
In
matrix
form
this
can
be
expressed
as

.
.
.
.
.
.
.
.
b
.
=
(7)
T
0
a
0

Here
a
is
a
4×
3
matrix
of
the
ane
coecients
a1,
a2,
a3
and
a4,
b
is
a
n×
3
matrix
of
the
non-ane
coecients
fbjgj=1:::n,
and
.
is
the
kernel
matrix
with
ij
=
(ji
-
j
j).
Solving
for
a
and
b
using
standard
algebra
yields
a
thin-plate
spline
transformation
that
will
interpolate
the
translation
at
the
control
points.
The
radial
basis
function
of
thin-plate
splines
is
de
ned
as

jsj2
log(jsj)
in
2D

(s)
=
(8)
js|
in
3D

In
our
experiments,
we
choose
(s)=
js|
since
we
are
registering
3D
volumes.

2.4.
Enforcement
of
smoothness
constraints
on
transformation
eld
Even
though
strict
criteria
is
used
in
selecting
matching
junctions,
there
can
still
be
false
matching
due
to
various
reasons,
such
as
noise
and
the
partial
volume
eect.
There
are
several
common
ways
to
remove
false
matching.
One
way24
is
to
nd
multiple
matches
for
each
control
point
in
the
source
volume
and
then
try
all
the
possible
combinations
of
the
matching
relations
to
nd
the
transformation
that
minimizes
the
dierence
between
the
source
and
target
volumes.
This
method
is
applicable
to
both
rigid
and
non-rigid
registration.
The
shortcoming
is
that
it
is
computationally
expensive.
A
second
method
is
to
estimate
a
transformation
eld,
i.e.
a
rigid
transformation,
and
then
check
the
registration
error
at
each
junction.
If
the
error
is
too
big,
then
it
is
a
false
match.
However
the
surface
interpolated
by
TPS
passes
through
the
control
points,
which
makes
this
method
not
suitable.
A
third
way
is
to
check
the
local
features
of
the
estimated
transformation
eld
at
each
junction,
and
remove
those
with
local
features
deviating
too
much
from
the
average.
In
the
proposed
approach,
the
third
method
is
used
and
the
local
feature
is
chosen
to
be
the
curvatures
of
the
transformation
eld.
The
curvatures
of
the
transformation
eld
in
both
horizontal
and
vertical
directions
are
computed
using
Laplacian
operator,
see
Equation
9-10.

O2Tx(x,
y,
z)=Tx(x
+1,
y,
z)+
Tx(x
-
1,
y,
z)+
Tx(x,
y
+1;z)+
(9)
Tx(x,
y
-
1;z)
-
4Tx(x,
y,
z)

O2Ty(x,
y,
z)=Ty(x
+1,
y,
z)+
Ty(x
-
1,
y,
z)+
Ty(x,
y
+1;z)+
(10)
Ty(x,
y
-
1;z)
-
4Ty(x,
y,
z)

where
Tx(x,
y,
z)
is
the
horizontal
component
of
the
displacement
vector
at
(x,
y,
z)
and
Ty(x,
y,
z)
is
the
vertical
component.
Due
to
the
anisotropic
nature
of
thick
CT
scans
on
which
the
experiments
are
carried
out,
the
displacement
vectors
in
the
neighboring
slices
are
not
used.
The
curvature
in
the
z
direction
is
not
computed
either.
It
is
assumed
that
the
real
transformation
eld
is
smooth,
therefore
its
curvature
should
be
small.
In
the
experiments,
the
mean
and
the
standard
deviation
of
the
curvatures
at
all
junctions
are
computed.
If
the
curvature
at
a
junction
is
larger
than
a
threshold
(1.0
in
our
experiments)
and
4
times
of
the
standard
deviation
of
the
curvatures
in
the
same
direction
at
all
junctions,
this
junction
is
removed.
This
process
is
repeated
iteratively
until
no
junctions
are
removed.

2.5.
Enforcement
of
vessel
constraints
In
landmark-based
registration,
it
is
desirable
to
have
as
less
false
matches
as
possible,
which
often
leads
to
a
strict
criteria
in
selecting
the
matching
pairs
of
landmarks.
On
the
other
hand,
it
is
also
important
to
have
enough
matching
landmarks
to
get
an
accurate
estimate
of
the
transformation.
This
means
the
criteria
should
B

A
A
A
B
B
vp
t
a
b
t
t
l
(a) (b)
A.
B0
Figure
1.
(a)
Aperture
problem
in
vessel
matching.
AB
is
a
vessel
segment
in
the
source
volume.
is
the
vessel

B00
segment
in
the
target
volume.
Due
to
the
partial
volume
eect,
the
matching
segment
B.
does
not
show
up.
The
vessel
segment
AB
is
matched
to
A.
B.
,
resulting
in
an
inaccurate
transformation
vector
AA.
.
However
the
translation
component
in
the
direction
of
AA0.
is
accurate.
(b)
Adjustment
to
the
transformation
eld.
v
is
a
vessel
and
l
is
the
normal
direction
of
v.
p
is
the
middle
location
of
vessel
v.
When
j(t
-
t.
)
·
lj,
shown
as
jabj,
is
larger
than
0.5,
an
additional

pair
of
control
points
is
added
to
the
TPS
interpolation
such
that
vector
twill
be
moved
to
t.
The
projection
of
ton
l
is
the
same
as
that
of
t.

not
be
too
strict.
Therefore,
there
is
a
dilemma.
In
the
registration
of
lung
volumes,
additional
information
can
be
obtained
from
the
matching
between
vessels
in
the
area
where
junctions
are
sparse
to
improve
the
registration.

A
vessel
covers
larger
area
therefore
the
matching
between
vessels
is
more
reliable
than
that
between
junctions.
In
the
experiments,
the
top
50%
of
vessels
are
selected
according
to
the
intensity
correlation.
However
there
is
an
aperture
problem
when
using
the
matching
between
vessels
to
estimate
the
displacement
vectors
due
to
the
linear
nature
of
the
vessel
segments
and
the
partial
volume
eect.
It
is
similar
to
the
aperture
problem
in
optical
ow.
In
the
proposed
approach,
we
only
trace
the
linear
vessel
segments
within
a
single
plane.
However
a
real
vessel
may
show
up
in
two
or
more
slices
with
each
slice
showing
a
part
of
it.
This
situation
may
lead
to
inaccuracy
in
matching,
see
Figure
1-(a).
AB
is
a
vessel
segment
in
the
source
volume.
A.
B.
is
the
vessel
segment
shown
in
the
target
volume.
The
matching
segment
B0B0.
does
not
show
up,
therefore
vessel
segment
AB
is
matched
to
A.
B0,
resulting
in
an
inaccurate
displacement
vector
AA.
.
However
the
translation
component
in
the
direction
of
AA0.
is
accurate,
which
can
be
used
to
improve
the
registration.

To
improve
the
robustness
of
vessel
matching,
only
those
vessels
that
satisfy
the
constraints
in
width,
length
and
intensity
are
selected.
In
the
experiments,
those
segments
with
width
larger
than
one
voxel,
length
longer
than
20
voxels,
and
mean
intensity
higher
than
40
are
selected.
Compared
with
junctions,
vessel
segments
are
easier
to
detect
(they
can
be
easily
traced
along
vessel
directions16).
By
using
linear
vessel
segments,
the
matching
relation
is
not
based
on
a
small
local
region
as
the
case
of
junctions,
but
based
on
the
matching
of
the
whole
vessels
thus
improving
the
robustness
of
the
matching.
To
improve
the
speed
and
robustness
of
the
search
for
matching
vessels,
pyramids
of
both
the
source
and
target
volumes
are
created.
The
search
starts
on
the
top
and
goes
down
to
the
bottom
of
the
pyramids.

As
discussed
earlier,
the
translation
in
the
normal
direction
of
vessels
can
be
used
to
improve
the
registration.
This
is
done
by
adding
additional
control
points
to
the
TPS
interpolation
if
there
is
a
big
dierence
in
the
projection
onto
the
normal
direction
of
vessels
between
the
displacement
vectors
estimated
from
vessel
matching
and
the
displacement
vectors
estimated
from
junctions.
Let
l
be
the
unit
normal
vector
on
the
slice
plane
of
a
vessel
v,
and
t
be
the
translation
vector
between
p
and
its
match.
Let
p
be
the
location
of
the
point
at
the
center
of
v
and
t.
be
the
translation
vector
at
p
estimated
from
junctions.
When
j(t.
-
t)
·
lj,
see
Figure
1-(b),
is
larger

than
0.5,
a
pair
of
control
points
(p,
p0)
is
added
into
the
set
of
junction
pairs.
pis
de
ned
as

p
=
p
+
t.
+
((t
-
t0)
·
l)l
(11)

where
t
is
the
translation
vector
estimated
from
vessel
matching.
After
adding
additional
control
points,
a
similar
iterative
process
as
discussed
in
section
2.4
is
applied
to
further
remove
the
false
matching.
(a)
(b)
Figure
2.
The
left
gure
shows
the
vessels
in
source
slice.
The
right
gure
shows
their
matches
in
a
target
slice.
Due
to
the
fact
that
the
source
vessels
and
their
matches
are
not
necessarily
on
the
same
slice,
the
match
of
some
vessels
in
(a)
is
not
shown
in
(b),
vice
versa.

3.
RESULTS
The
registration
scheme
was
tried
on
6
pairs
of
temporal
CT
scans.
We
use
the
normalized
sum
of
absolute
distance
(NSAD)
between
the
transformed
source
volume
and
the
target
volume
to
measure
the
registration
error.
The
NSAD
is
de
ned
by
the
following
equation:

NSAD
=
j(I.
(x,
y,
z)
-
1)
-
(It(x,
y,
z)
-
2)|
(12)
s
N

(x;y;z)2W

where
W
is
a
local
window
centered
at
(x,
y,
z),
N
is
the
number
of
voxels
in
W
,
1
and
2
are
the
mean
intensity
of
I.
and
It
in
W
.
I.
and
It
are
the
transformed
source
volume
and
the
target
volume
respectively.
Since
the

ss

intensity
of
the
same
structure
may
be
on
dierent
levels
in
the
source
and
target
volumes,
by
using
this
distance
measure,
the
uence
in
of
the
mean
intensity
is
eliminated.
To
evaluate
the
performance,
the
proposed
algorithm
is
compared
with
three
other
registration
algorithms.
The
three
algorithms
are
3D
surface-based
registration,25
3D
voxel-based
registration,26
3D
non-rigid
registration
based
on
normalized
mutual
information.27,
28

In
order
to
evaluate
how
well
the
proposed
registration
algorithm
recovers
the
transformation
eld
between
temporal
CT
scans,
synthetic
volumes
are
created
by
applying
a
known
non-rigid
transformation
to
six
clinical
CT
scans,
and
then
the
registration
methods
are
used
to
register
the
deformed
CT
scans
with
the
original
ones.
Since
the
transformation
between
real
temporal
CT
scans
is
not
known
and
that
the
synthetic
eld
used
in
the
experiment
should
be
close
to
the
transformation
eld
that
happens
in
the
real
situation
to
make
the
experiment
valid,
the
synthetic
transformation
eld
is
estimated
by
registering
the
six
pairs
of
real
temporal
CT
scans.
Table
1
shows
the
quantitative
evaluation
of
the
proposed
algorithm.
It
can
be
seen
from
the
rst
part
of
Table
1
that
NSAD
measure
between
the
source
and
target
volumes
after
registration
by
the
proposed
algorithm
is
within
range
of
[0:93
2:87],
which
is
much
smaller
than
the
distance
obtained
using
the
three
other
registration
methods.
The
second
part
of
Table
1
shows
the
dierence
between
the
estimated
transformation
eld
and
the
known
one.
It
shows
the
mean
length
dierence
(measured
in
voxels),
the
deviation
of
the
length
dierence,
the
relative
dierence
which
is
the
dierence
in
length
divided
by
the
length
of
vectors
in
the
known
transformation
eld,
the
deviation
of
the
relative
dierence,
orientation
dierence
in
radian,
and
the
deviation
of
orientation
dierence
respectively.
We
can
see
the
mean
length
dierence
is
less
than
half
voxel,
the
mean
relative
dierence
is
less
than
6
percents,
and
the
mean
orientation
dierence
is
less
than
0.16
radians
or
10
degrees.
Therefore,
the
results
demonstrate
the
accuracy
of
the
proposed
approach.
Figure
3
shows
both
the
synthetic
transformation
elds
(rigid
and
radial)
and
the
estimated
ones.
We
can
see
that
the
estimated
transformation
elds
are
almost
identical
to
the
known
ones.
In
order
to
evaluate
the
robustness
of
the
registration
method
against
noise
more
Normalized
Sum
of
Absolute
Distance
case
1
case
2
case
3
case
4
case
5
case
6
Initial
alignment
12.935934
10.184602
4.038031
4.592606
10.818130
12.540091
Our
method
2.874246
1.759547
0.933038
1.105014
2.199541
1.617745
3D
surface
12.264107
8.286962
3.624727
3.954760
8.645557
10.435795
3D
voxel
10.850707
8.879189
3.411876
4.110611
8.325506
11.212677
3D
NMI
10.970194
7.525686
2.942583
3.668975
8.144775
8.570295
Dierence
of
Transformation
Vectors
case
1
case
2
case
3
case
4
case
5
case
6
Length
dierence
(mean)
0.375367
0.428600
0.349846
0.325419
0.383261
0.250679
Length
dierence
(dev)
0.533279
0.461256
0.473773
0.344143
0.403307
0.225654
Ralative
dierence
(mean)
0.049537
0.056607
0.054391
0.049650
0.056897
0.045490
Ralative
dierence
(dev)
0.064817
0.084736
0.098690
0.069591
0.074486
0.066269
Orientation
dierence
(mean)
0.079209
0.075370
0.083442
0.071492
0.087357
0.060312
Orientation
dierence
(dev)
0.108536
0.117759
0.143446
0.159750
0.120957
0.105408

Table
1.
Results
of
evaluating
the
proposed
approach
in
recovering
known
transformation
eld.
It
can
be
seen
from
the
rst
part
that
distance
between
the
source
and
target
volumes
after
registration
by
our
algorithms
is
within
range
of

[0:93
2:87],
which
is
much
smaller
than
the
distance
obtained
using
the
other
three
registration
methods.
From
the
second
part
of
this
table,
We
can
see
the
mean
dierence
in
length
is
less
than
half
voxel,
the
mean
relative
error
in
length
is
less
than
6
percents,
and
the
mean
orientation
error
is
less
than
0.16
radians
or
10
degrees.
(a)
(b)
Figure
3.
The
result
of
registration
on
image
deformed
by
synthetic
transformation
eld.
(a)
known
non-rigid
transform
ation
eld.
(b)
estimated
non-rigid
eld.

comprehensively,
additive
zero-mean
Gaussian
noise
at
multiple
levels
is
added
to
the
synthetic
deformed
volumes.
Figure
4
shows
the
mean
and
deviation
of
the
magnitude
dierence
of
the
displacement
vectors.
It
can
be
seen
that
the
registration
algorithm
is
quite
robust
up
to
10
dB
(signal
to
noise
ratio).

4.
CONCLUSION
In
this
paper,
a
general
registration
framework
that
uses
both
junctions
and
vessels
are
proposed.
The
landmarks
(junctions
and
linear
vessel
segments)
are
obtained
from
the
vessel
network
after
enhancement.
We
use
the
vessel
enhancement
lter
proposed
in
our
previous
work,16
which
can
distinguish
between
junctions
and
nodules,
thus
 2
1.6
1.8
1.4
1.6
1.2
0 5 10 15 20

0 5 10 15 20

Mean normal of difference vector

1.4
1.2
1
Angle of difference vector
1
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2Signal to noise ratio (SNR)Signal to noise ratio (SNR)
(a)
(b)
Figure
4.
Evaluation
of
the
registration
algorithm
with
respect
to
noise.
(a)
mean
magnitude
of
dierence
vector
between
the
transformation
elds.
(d)
the
standard
deviation
of
the
magnitude
of
the
dierence
vectors
between
the
transformation
elds.
It
can
be
seen
that
the
registration
algorithm
is
quite
robust
up
to
10
dB.

the
negative
impact
of
new
nodules
are
suppressed.
In
the
segmented
vessel
network,
junctions
are
selected
by
checking
the
ratio
of
eigenvalues
of
the
gradient
correlation
matrix.
The
matching
between
junctions
is
built
by
searching
in
the
target
volume
within
a
local
window
after
initial
alignment
of
the
source
and
target
volumes.
The
false
matching
of
junctions
are
iteratively
removed
using
the
local
feature
of
the
transformation
eld.
Besides
junctions,
additional
constraints
from
vessels
are
incorporated
to
improve
the
registration.
The
matching
between
vessels
are
obtained
by
deforming
the
contour
of
vessels
to
their
matches
under
the
guidance
of
an
energy
function.
The
transformation
eld
is
interpolated
using
thin
plate
splines.
Various
experiments
show
the
the
proposed
algorithm
is
accurate
in
estimating
the
non-rigid
transformation
eld
between
temporal
CT
scans
and
also
robust
against
noise.
The
experiment
with
synthetic
nodules
demonstrates
the
robustness
of
the
proposed
method
against
new
nodules.
Future
work
would
be
to
evaluate
the
registration
on
high-resolution
CT
scans
and
check
its
application
in
the
diagnosis
of
lung
disease
such
as
detection
of
new
nodules
and
other
blood
vessel
related
diseases.
REFERENCES

1.
C.
L.
Novak,
H.
Shen,
B.
L.
Odry,
J.
P.
Ko,
and
D.
P.
Naidich,
\System
for
automatic
detection
of
lung
nodules
exhibiting
growth,
in
Proc.
of
SPIE
Medical
Imaging:
Image
Processing,
J.
M.
Fitzpatrick
and
M.
Sonka,
eds.,
5370,
pp.
10{21,
May
2004.
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