Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing
Cell,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 1, 2024
Glioblastomas
are
invasive
brain
tumors
with
high
therapeutic
resistance.
Neuron-to-glioma
synapses
have
been
shown
to
promote
glioblastoma
progression.
However,
a
characterization
of
tumor-connected
neurons
has
hampered
by
lack
technologies.
Here,
we
adapted
retrograde
tracing
using
rabies
viruses
investigate
and
manipulate
neuron-tumor
networks.
Glioblastoma
rapidly
integrated
into
neural
circuits
across
the
brain,
engaging
in
widespread
functional
communication,
cholinergic
driving
invasion.
We
uncovered
patient-specific
tumor-cell-state-dependent
differences
synaptogenic
gene
expression
associated
connectivity
subsequent
invasiveness.
Importantly,
radiotherapy
enhanced
increased
neuronal
activity.
In
turn,
simultaneous
activity
inhibition
showed
effects,
indicative
role
for
neuron-to-glioma
contributing
Lastly,
rabies-mediated
genetic
ablation
halted
progression,
offering
viral
strategy
tackle
glioblastoma.
Together,
this
study
provides
framework
comprehensively
characterize
networks
target
Язык: Английский
Assessment of Tumor Cell Invasion and Radiotherapy Response in Experimental Glioma by Magnetic Resonance Elastography
Journal of Magnetic Resonance Imaging,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 23, 2024
Background
Gliomas
are
highly
invasive
brain
neoplasms.
MRI
is
the
most
important
tool
to
diagnose
and
monitor
glioma
but
has
shortcomings.
In
particular,
assessment
of
tumor
cell
invasion
insufficient.
This
a
clinical
dilemma,
as
recurrence
can
arise
from
MRI‐occult
invasion.
Hypothesis
Tumor
invasion,
growth
radiotherapy
alter
parenchymal
microstructure
thus
assessable
by
diffusion
tensor
imaging
(DTI)
MR
elastography
(MRE).
Study
Type
Experimental,
animal
model.
Animal
Model
Twenty‐three
male
NMRI
nude
mice
orthotopically
implanted
with
S24
patient‐derived
cells
(experimental
mice)
9
stereotactically
injected
1
μL
PBS
(sham‐injected
mice).
Field
Strength/Sequence
2D
3D
T2‐weighted
rapid
acquisition
refocused
echoes
(RARE),
echo
planar
(EPI)
DTI,
multi‐slice
multi‐echo
(MSME)
T2
relaxometry,
MSME
MRE
at
900
Hz
acquired
9.4
T
(675
mT/m
gradient
strength).
Assessment
Longitudinal
4‐weekly
was
performed
for
up
4
months.
volume
assessed
in
experimental
(n
=
10
treatment‐control,
n
13
radiotherapy).
The
subgroup
5
sham‐injected
underwent
irradiation
(3
×
6
Gy)
weeks
post‐implantation/sham
injection.
MRI‐/MRE‐parameters
were
corpus
callosum
core/injection
tract.
Imaging
data
correlated
light
sheet
microscopy
(LSM)
histology.
Statistical
Tests
Paired
unpaired
t
‐tests,
P
‐value
≤0.05
considered
significant.
Results
From
week
8,
significant
callosal
stiffening
(4.44
±
0.22
vs.
5.31
0.29
kPa)
detected
correlating
LSM‐proven
occult
all
other
metrics.
Histologically
proven
tissue
destruction
core
led
an
increased
relaxation
time
(41.65
0.34
44.83
0.66
msec)
ADC
(610.2
12.27
711.2
13.42
−6
mm
2
/s)
softening
(5.51
0.30
4.24
8
12.
Radiotherapy
slowed
progression.
Data
Conclusion
promising
key
characteristics.
Evidence
Level
NA
Technical
Efficacy
Stage
Язык: Английский
Beyond the EPR effect: Intravital microscopy analysis of nanoparticle drug delivery to tumors
Advanced Drug Delivery Reviews,
Год журнала:
2025,
Номер
unknown, С. 115550 - 115550
Опубликована: Фев. 1, 2025
Язык: Английский
The characteristics of capillary remodeling in cerebellar neurodegenerative diseases revealed through layered imaging and stereoscopic analysis
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 24, 2025
Abstract
Neurodegenerative
diseases
refer
to
a
group
of
clinical
conditions
characterized
by
progressive
neuronal
loss,
resulting
in
impaired
brain
structural
integrity
and
functional
abnormalities.
These
can
lead
widespread
cerebrovascular
remodeling;
however,
the
spatial
remodeling
features
capillaries
with
diameters
≤
10
μm
remain
poorly
understood,
particularly
regard
changes
relationship
between
neurons
capillaries.
In
this
study,
we
first
developed
double-fluorescent
transgenic
mouse
model
cerebellar
neurodegenerative
disease
(CBND),
PCKO
TomatoVessel
Green
mouse,
which
Purkinje
cells
(PCs)
cerebellum
express
red
fluorescent
protein,
while
system
expresses
green
protein
(with
no
differentiation
arteries
veins).
Subsequently,
employed
whole-brain
clearing
combined
Amira/Imaris
conduct
three-dimensional
layered
imaging
computational
analysis
network
both
adult
control
mice.
A
total
181744
PCs
vessels
length
17.7363
meters,
266175
segments,
volume
0.5314
mm³
were
analyzed.
Compared
Control
mice,
mice
exhibited
93%
reduction
count
PCs,
97%
69%
volume,
58%
decrease
vessel
length,
52%
vascular
volume.
Depth
revealed
55%,
58%,
capillary
chord
curved
tortuosity,
respectively,
statistical
differences
node
or
φ
θ
directional
values.
Further
fraction
(VF)
59%
increase
capillary-cerebellum
VF,
PC-vessel
PC-capillary
PC-noncapillary
VF
decreased
95%,
96%,
respectively.
Additionally,
shortest
distance
vessel-cerebellum
noncapillary-cerebellum
showed
differences.
Our
results
indicated
that
significantly
lost,
their
topology
remained
stable,
decreasing
from
16
7
μm.
This
process
is
central
pathogenesis
CBND.
Furthermore,
may
serve
as
biological
markers
for
early
diagnosis
findings
provide
foundation
development
targeted
therapies
Short
abstract
Cerebrovascular
caused
be
used
diagnosis,
but
its
characteristics
are
unclear.
research
constructed
disease,
then
adopted
whole
transparency
system.
m,
number
segments
mm
3
analyzed
stratified
analysis.
3.15
TB
data
lost
although
stable.
blood
μm,
identifying
feature
neurovascular
disease.
The
cell-vessel
diseases.
Язык: Английский
Reconstructing the Single-Cell Spatiotemporal Dynamics of Glioblastoma Invasion
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 25, 2025
Abstract
Glioblastoma
invasion
into
healthy
brain
tissue
remains
a
major
barrier
to
effective
treatment,
yet
current
models
fail
capture
its
full
complexity
in
scalable
and
patient-specific
manner.
Here,
we
introduce
GlioTrace,
novel
ex
vivo
imaging
AI-based
analytical
framework
that
enables
real-time,
spatiotemporal
tracking
of
glioblastoma
dynamics
patient-derived
glioma
cell
culture
xenograft
(PDCX)
slices.
By
integrating
whole-specimen
confocal
microscopy,
vascular
counterstaining,
an
advanced
computational
pipeline
combining
convolutional
neural
networks
Hidden
Markov
Models,
GlioTrace
identifies
distinct
modes—including
dynamic
morphological
switching,
vessel-guided
migration,
immune
interactions—and
quantifies
variations
plasticity.
Using
demonstrate
targeted
therapies
can
selectively
modulate
phenotypes,
revealing
spatially
temporally
drug
responses.
This
platform
provides
unprecedented
window
progression
treatment
response,
offering
powerful
tool
for
precision
oncology
anti-invasion
therapeutic
development.
Язык: Английский
Predicting glioblastoma progression using MR diffusion tensor imaging: A systematic review
Journal of Neuroimaging,
Год журнала:
2024,
Номер
35(1)
Опубликована: Дек. 9, 2024
Abstract
Background
and
purpose
Despite
multimodal
treatment
of
glioblastoma
(GBM),
recurrence
beyond
the
initial
tumor
volume
is
inevitable.
Moreover,
conventional
MRI
has
shortcomings
that
hinder
early
detection
occult
white
matter
tract
infiltration
by
tumor,
but
diffusion
tensor
imaging
(DTI)
a
sensitive
probe
for
assessing
microstructural
changes,
facilitating
identification
progression
before
standard
imaging.
This
sensitivity
makes
DTI
valuable
tool
predicting
recurrence.
A
systematic
review
was
therefore
conducted
to
investigate
how
DTI,
in
comparison
MRI,
can
be
used
GBM
progression.
Methods
We
queried
three
databases
(PubMed,
Web
Science,
Scopus)
using
search
terms:
(diffusion
OR
DTI)
AND
(glioblastoma
GBM)
(recurrence
progression).
For
included
studies,
data
pertaining
study
type,
number
patients,
type(s),
DTI‐related
metrics
were
extracted.
Results
In
all,
16
studies
included,
from
which
there
394
patients
total.
Six
reported
decreased
fractional
anisotropy
regions,
2
described
utility
connectomics/tractography
migratory
pathways
site
Three
evidence
visible
on
Conclusions
These
findings
suggest
may
useful
guiding
surgical
radiotherapy
planning
informing
long‐term
surveillance.
Understanding
current
state
literature
these
metrics’
trends
crucial,
particularly
as
increasingly
treatment‐guiding
modality.
Язык: Английский
Advances in Deep Brain Imaging with Quantum Dots: Structural, Functional, and Disease-Specific Roles
Photonics,
Год журнала:
2024,
Номер
12(1), С. 3 - 3
Опубликована: Дек. 24, 2024
Quantum
dots
(QDs)
have
emerged
as
promising
tools
in
advancing
multiphoton
microscopy
(MPM)
for
deep
brain
imaging,
addressing
long-standing
challenges
resolution,
penetration
depth,
and
light–tissue
interactions.
MPM,
which
relies
on
nonlinear
photon
absorption,
enables
fluorescence
imaging
within
defined
volumes,
effectively
reducing
background
noise
photobleaching.
However,
achieving
greater
depths
remains
limited
by
light
scattering
compounded
the
need
balanced
laser
power
to
avoid
tissue
damage.
QDs,
nanoscale
semiconductor
particles
with
unique
optical
properties,
offer
substantial
advantages
over
traditional
fluorophores,
including
high
quantum
yields,
large
absorption
cross-sections,
superior
photostability,
tunable
emission
spectra.
These
properties
enhance
signal
ratio
at
increased
reduce
effects,
making
QDs
ideal
subcortical
regions
like
hippocampus
without
extensive
microscope
modifications.
Studies
demonstrated
capability
of
achieve
up
2100
μm,
far
exceeding
that
conventional
fluorophores.
Beyond
structural
facilitate
functional
applications,
such
high-resolution
tracking
hemodynamic
responses
neural
activity,
supporting
investigations
neuronal
dynamics
blood
flow
vivo.
Their
stability
long-term,
targeted
drug
delivery
photodynamic
therapy,
presenting
potential
therapeutic
applications
treating
tumors,
Alzheimer’s
disease,
traumatic
injury.
This
review
highlights
impact
their
effectiveness
overcoming
attenuation
tissue,
expanding
role
diagnosing
neurological
disorders,
positioning
them
transformative
agents
both
intervention.
Язык: Английский