Chemotherapy-induced
cognitive
impairment
(CICI),
often
referred
to
as
"chemobrain,"
significantly
affects
the
quality
of
life
in
cancer
survivors.
Although
traditionally
attributed
neuronal
toxicity,
emerging
evidence
suggests
a
key
role
cerebrovascular
dysfunction
its
pathogenesis.
We
hypothesized
that
paclitaxel
(PTX,
Taxol)
treatment
induces
long-term
dysfunction,
including
microvascular
rarefaction,
impaired
neurovascular
coupling
(NVC),
and
altered
cerebral
blood
flow
(CBF),
which
contribute
CICI.
Using
clinically
relevant
PTX
regimen
non-tumor-bearing
mice,
we
evaluated
effects
on
health.
Ultrasound
localization
microscopy
(ULM)
functional
ultrasound
imaging
(fUS)
were
employed
assess
density,
CBF,
NVC.
resulted
significant
reduction
density
cortex
hippocampus,
regions
involved
function.
reduced
velocity
middle
artery.
Moreover,
NVC
responses,
evidenced
by
diminished
CBF
increase
response
whisker
stimulation,
indicative
reactive
hyperemia.
In
conclusion,
these
findings
demonstrate
long-lasting
NVC,
dynamics,
likely
This
study
underscores
critical
health
function
highlights
potential
targeting
pathways
therapeutic
approach
for
mitigating
chemotherapy-induced
deficits.
Ultrasound
localization
microscopy
(ULM)
is
an
emerging
imaging
modality
that
resolves
microvasculature
in
deep
tissues
with
high
spatial
resolution.
However,
existing
preclinical
ULM
applications
are
largely
constrained
to
anesthetized
animals,
introducing
confounding
vascular
effects
such
as
vasodilation
and
altered
hemodynamics.
As
such,
quantifications
(e.g.,
vessel
diameter,
density,
flow
velocity)
may
be
confounded
by
the
use
of
anesthesia,
undermining
usefulness
practice.
Here
we
introduce
a
method
address
this
limitation
achieve
awake
mouse
brain.
Pupillary
monitoring
was
used
support
presence
state
during
imaging.
Vasodilation
induced
isoflurane
observed
ULM.
Upon
recovery
state,
reductions
density
velocity
were
across
different
brain
regions.
In
cortex,
more
pronounced
on
venous
than
arterial
flow.
addition,
serial
vivo
same
animal
at
weekly
intervals
demonstrated
highly
robust
longitudinal
capability
proposed
technique.
The
consistency
further
verified
through
quantitative
analysis
individual
vessels,
cortical
regions
arteries
veins,
subcortical
This
study
demonstrates
brain,
which
crucial
for
many
require
behaving
animals.
European Radiology Experimental,
Год журнала:
2025,
Номер
9(1)
Опубликована: Март 5, 2025
We
studied
the
microvascular
structure
and
function
of
in
situ
glioblastoma
using
ultrasound
localization
microscopy
(ULM).
The
vivo
study
was
conducted
via
craniotomy
six
Sprague-Dawley
rats.
Capillary
pattern,
capillary
hemodynamics,
functional
quantitative
parameters
were
compared
among
tumor
core,
invasive
zone,
normal
brain
tissue
with
ex
micro-computed
tomography
(micro-CT)
scanning
electron
microscopy.
Correlations
between
histopathological
vascular
density
(VD-H),
proliferation
index,
maturity
index
(VMI-H)
evaluated.
Kruskal-Wallis
H,
ANOVA,
Mann-Whitney
U,
Pearson,
Spearman
correlation
statistics
used.
Compared
to
zone
exhibited
higher
microvascularity
structural
disorder
complexity,
increased
hemodynamic
heterogeneity,
local
blood
flow
perfusion
(p
≤
0.033),
slightly
lower
average
velocity
=
0.873).
Significant
differences
observed
across
all
0.001).
ULM
demonstrated
microstructural
resolution
micro-CT
a
nonsignificant
difference
correlated
VD-H
(r
0.781,
p
<
Vessel
diameter
0.960,
0.001),
curvature
0.438,
0.047),
0.487,
0.025),
volume
0.858,
0.001)
index.
Vascular
-0.444,
0.044)
fractal
dimension
-0.933,
VMI-H.
provided
high-resolution,
noninvasive
imaging
microvascularity,
offering
insights
into
structural/functional
abnormalities.
technology
based
on
ultrafast
can
accurately
quantify
microvessels
glioblastoma,
providing
new
method
for
evaluating
effectiveness
antiangiogenic
therapy
visualizing
disease
progression.
This
may
facilitate
early
therapeutic
assessment.
reliably
captures
structures
features
Micro-CT
validated
its
non-invasion
characterization.
is
expected
effectively
evaluate
anti-vascular
response.
Chemotherapy-induced
cognitive
impairment
(CICI),
often
referred
to
as
"chemobrain,"
significantly
affects
the
quality
of
life
in
cancer
survivors.
Although
traditionally
attributed
neuronal
toxicity,
emerging
evidence
suggests
a
key
role
cerebrovascular
dysfunction
its
pathogenesis.
We
hypothesized
that
paclitaxel
(PTX,
Taxol)
treatment
induces
long-term
dysfunction,
including
microvascular
rarefaction,
impaired
neurovascular
coupling
(NVC),
and
altered
cerebral
blood
flow
(CBF),
which
contribute
CICI.
Using
clinically
relevant
PTX
regimen
non-tumor-bearing
mice,
we
evaluated
effects
on
health.
Ultrasound
localization
microscopy
(ULM)
functional
ultrasound
imaging
(fUS)
were
employed
assess
density,
CBF,
NVC.
resulted
significant
reduction
density
cortex
hippocampus,
regions
involved
function.
reduced
velocity
middle
artery.
Moreover,
NVC
responses,
evidenced
by
diminished
CBF
increase
response
whisker
stimulation,
indicative
reactive
hyperemia.
In
conclusion,
these
findings
demonstrate
long-lasting
NVC,
dynamics,
likely
This
study
underscores
critical
health
function
highlights
potential
targeting
pathways
therapeutic
approach
for
mitigating
chemotherapy-induced
deficits.
