1. Pearls and Pitfalls of MR Diffusion
in Clinical Neurology
Dr.
Alberto
Bizzi
Neuroradiology
Unit
Fondazione
IRCCS
Istituto
Neurologico
Carlo
Besta
Milan,
Italy
Email:
alberto_bizzi@fastwebnet.it
Diffusion
Tensor
Imaging
(DTI)(1)
measures
the
effects
of
tissue
microstructure
on
the
random
walks
(brownian
motion)
of
water
molecules
in
the
brain.
In
tissues
with
an
orderly
oriented
microstructure,
such
as
the
cerebral
white
matter,
the
measured
diffusivity
of
water
varies
with
the
tissue’s
orientation
(anisotropic
diffusion).
Water
diffuses
fastest
along
the
principal
direction
of
the
fibers,
and
slowest
along
the
cross-­‐sectional
plane.
The
DTI
model
provides
the
required
information
to
construct
a
diffusion
ellipsoid
in
each
voxel
of
an
imaging
volume.
DTI
measures
the
diffusivities
of
water
molecules
along
the
three
orthogonal
axes
of
the
ellipsoid
(eigenvalues)
and
their
average
(mean
diffusivity).
Fractional
anisotropy
is
a
measure
of
eccentricity
of
the
displacement
of
water
molecules.
In
the
healthy
human
brain
probably
the
most
relevant
factor
affecting
fractional
anisotropy
is
the
intravoxel
orientation
coherence
of
white
matter
fibers(2).
There
are
three
main
imaging
output
of
DTI
MR
imaging:
quantitative
parametric
maps
displayed
in
gray
scale
(i.e.
fractional
anisotropy
maps),
color
maps
showing
the
principal
orientation
of
diffusion
for
each
voxel
and
3
dimensional
maps
showing
virtual
dissection
of
tracts
with
streamline
tracking
methods.
In
the
interest
of
time
in
the
oral
presentation
we’ll
focus
on
diffusion
MR
Tractography
and
its
clinical
application
in
brain
tumors,
stroke,
multiple
sclerosis,
prion
disorders
and
neurodegenerative
diseases
(Alzheimer,
Amyotrophic
Lateral
Sclerosis).
The
aim
of
MR
Tractography
or
fiber
tracking
is
to
infer
the
three-­‐dimensional
trajectories
of
white
matter
bundles
by
piecing

2. together
discrete
estimates
of
the
underlying
continuous
fiber
orientation
field
measured
non-­‐invasively
with
DTI
data(3,
4).
Fiber
tracking
algorithms
can
be
broadly
classified
into
two
types:
deterministic
and
probabilistic.
Few
DTI
Tractography
atlases
for
virtual
in
vivo
dissection
of
the
principal
human
white
matter
tracts
using
a
deterministic
approach
have
been
recently
published(5-­‐7).
Few
limitations
of
fiber
tracking
performed
with
the
deterministic
approach
motivated
the
development
of
probabilistic
tracking
algorithms(5).
It
is
very
important
to
understand
well
the
inherent
limitations
of
all
methods
of
DTI-­‐based
virtual
dissections
and
measurements.
One
important
limitation
is
that
in
each
voxel
the
eigen
vector
is
the
average
of
the
orientation
of
all
bundles
included
in
the
voxel.
In
volumes
of
white
matter
with
many
crossing
bundles,
as
in
the
frontal
and
parietal
paraventricular
white
matter,
fractional
anisotropy
is
low
and
the
degree
of
uncertainty
in
the
estimation
of
bundle
orientation
increases.
An
attempt
to
overcome
the
limitation
of
crossing
fibers
has
been
addressed
with
the
development
of
more
sophisticated
imaging
acquisition
schemes
using
high
angular
resolution
diffusion
imaging
(HARDI)(6).
It
is
important
to
emphasize
that,
given
the
relative
size
differences
between
the
individual
axons
(1–5
micron)
and
voxels
(2–3
mm)
size,
it
is
possible
to
observe
white
matter
anatomy
only
from
a
macroscopic
point
of
view
with
MR
Tractography.
Notwithstanding,
the
anatomic
detail
provided
by
MR
Tractography
with
10-­‐15
min
of
MR
acquisition
is
unparalleled.
Encouraging
results
with
DTI
have
been
reported
in
several
neurological
disorders:
brain
tumors,
stroke,
multiple
sclerosis,
amyotrophic
lateral
sclerosis,
Alzheimer
disease
and
other
dementias.
In
the
interest
of
time
we’ll
focus
on
the
application
that
is
probably
closer
to
become
of
clinical
use:
diffusion
MR
Tractography
in
presurgical
planning.
The
integration
of
functional
data
acquired
with
fMRI
and
MEG
into
the
navigational
data
sets
has
improved
quick
identification
of
eloquent
cortex
with
intraoperative
ESM
in
the
operating
room.
To
avoid
postoperative
neurological
deficits,
however,
it
is
also
necessary
to
preserve
the
white
matter
tracts
connecting
eloquent
cortex.

3. Diffusion
MR
Tractography
has
recently
emerged
as
potentially
valuable
clinical
tool
for
presurgical
planning(7-­‐9)
and
intraoperative
imaging-­‐guided
navigation
in
the
operating
room(10).
Diffusion
MR
Tractography
can
provide
the
neurosurgeon
with
additional
information
about
brain
anatomy,
pathology
and
architecture
that
conventional
MRI
methods
cannot.
Fig.
1
-­‐
Directionally
encoded
color
maps
in
a
65
years
old
male
with
glioblastoma
multiforme
in
the
left
dorsolateral
prefrontal
region.
The
mass
has
infiltrated
the
superior
longitudinal
fasciculus,
including
the
arcuate
fasciculus
(displayed
in
green,
see
cursor).
The
directionally
encoded
color
maps,
with
hues
reflecting
tensor
orientation
and
intensity
weighted
by
fractional
anisotropy,
provides
an
aesthetic
and
informative
synthesis
of
tissue
microstructure
and
architecture.
The
color
maps
are
a
promising
tool
for
delineation
of
tumor
extent
and
infiltration.
DTI
color
maps
indicate
whether
a
mass
is
displacing,
infiltrating
or
destroying
the
main
white
matter
tracts(11).
MR
Tractography
can
be
used
to
virtually
dissect
functionally
critical
white
matter
tracts,
such
as
the
corticospinal
tract
and
the
arcuate
fasciculus
(AF),
enabling
the
neurosurgeon
to
identify
and
preserve
the
tract
during
resection(12).
It
has
been
shown
that
acquisition
of
DTI
color
maps
is
feasible
also
in
the
operating
room
with
intraoperative
1.5
Tesla
MR
scanners.
Intraoperative
DTI
can
depict
shifting
of
major
white
matter
tracts
that
may
occur
during
surgical
removal
of
the
mass.
It
has
been
shown
that
shifting
of
brain
structures
may
be

4. unpredictable,
therefore
intraoperative
updating
of
the
navigation
system
is
strongly
recommended(10).
Fig.
2
–
Streamlines
of
the
three
segments
of
the
left
arcuate
fasciculus
(AF:
long
segment
in
red,
anterior
in
green,
posterior
in
yellow)
are
displied
on
the
diffusion-­‐weighted
image
at
the
level
of
a
mass
in
the
left
posterior
mesial
temporal
lobe.
In
this
70
years-­‐old
male
with
glioblastoma
multiforme,
MR
Tractography
was
essential
to
demonstrate
that
the
mass
had
not
destroyed
but
only
displaced
the
AF
posteriorly
and
laterally.
Streamlines
of
the
AF
confirmed
that
most
of
the
fasciculus
was
intact.
Three
dimensional
objects
of
preoperative
virtually
dissected
tracts
can
be
reliably
integrated
into
a
standard
neuronavigation
system,
allowing
for
intraoperative
visualization
and
localization
of
the
main
tracts(13).
MR
Tractography
may
show
the
relationship
of
the
mass
to
the
virtually
dissected
AF.
Virtual
dissection
of
the
three
segments
of
the
AF
may
show
whether
the
mass
has
partially
interrupted
or
only
displaced
each
of
the
three
segments
of
the
AF.
Display
of
MR
Tractography
results
may
also
be
useful
in
the
operating
room
when
the
neurosurgeon
is
approaching
an
important
bundle
and
he
wants
to
reinforce
his
anatomical
orientation
in
the
operating
field
and
consider

5. whether
to
use
subcortical
ESM
to
test
the
functional
relevance
of
a
specific
tract(14).
Fig.
3
–
Streamlines
of
the
left
inferior
frontal
occipital
fasciculus
(IFOF)
and
fMRI
(sentence
comprehension
task)
are
overlaid
on
FLAIR
images,
neuronavigator-­‐
ready
for
guiding
surgery
in
the
operating
room.
In
this
62
years-­‐old
woman
with
fibrillary
astrocytoma
in
the
left
temporal
pole,
MR
Tractography
demonstrated
that
the
mass
had
partially
interrupted
the
uncinate
fasciculus
(UF,
not
shown),
while
the
IFOF
(in
pink)
appears
intact.
Note
the
close
relationship
of
the
left
IFOF
with
the
hyperintense
mass
in
the
temporal
pole.
Modern
cognitive
models
of
language
have
shown
that
there
is
a
lot
of
redundancy
in
the
language
network.
It
is
of
paramount
importance
to
identify
those
bundles
that
if
severed
may
cause
permanent
language
deficits.
Definition
of
which
bundles
are
functionally
eloquent
and
have
to
be
absolutely
spared
during
resection
remains
an
important
issue.
There
is
a
long
list
of
important
limitations(15).
Few
are
inherent
to
the
DTI
and
the
MR
Tractography
technology
and
they
must
be
well
understood

6. before
the
results
of
presurgical
MR
Tractography
dissections
can
be
safely
exported
to
the
operating
room.
It
is
not
yet
established
whether
resection
of
fibers
apparently
infiltrated
by
the
tumor
that
appear
to
be
interrupted
or
destroyed
on
diffusion
MR
Tractography
will
result
in
permanent
postoperative
neurologic
deficits(15).
Nevertheless,
it
should
be
established
whether
resection
of
fibers
that
on
MR
Tractography
appear
to
be
interrupted
within
the
tumor
will
cause
permanent
postoperative
deficits.
On
the
contrary,
it
has
been
shown
many
times
that
severing
of
the
pyramidal
tract
will
cause
hemiplegia.
Whether
severing
of
one
of
the
many
language
connections
will
cause
aphasia
is
currently
a
controversial
issue(16).
In
conclusion,
diffusion
MR
Tractography
has
emerged
as
a
valuable
tool
in
the
evaluation
of
motor
and
language
pathways
both
in
healthy
individuals
and
in
patients
with
neurological
disorders.
In
healthy
subjects
they
are
contributing
to
refine
current
cognitive
and
anatomic
models.
Not
only
they
have
confirmed
several
theories
about
language
processing,
but
they
have
also
raised
unexpected
important
questions.
In
patients
with
brain
tumors
they
have
obtained
recognition
as
valuable
presurgical
clinical
tools
in
the
determination
of
hemispheric
dominance
and
in
the
selection
of
candidates
who
may
benefit
from
awake
craniotomy.

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