Mathematics,
Journal Year:
2022,
Volume and Issue:
10(23), P. 4593 - 4593
Published: Dec. 4, 2022
The
blood–brain
barrier
is
a
unique
physiological
structure
acting
as
filter
for
every
molecule
reaching
the
brain
through
blood.
For
this
reason,
an
effective
pharmacologic
treatment
supplied
to
patient
by
systemic
circulation
should
first
be
capable
of
crossing
barrier.
Standard
cell
cultures
(or
those
based
on
microfluidic
devices)
and
animal
models
have
been
used
study
human
Unfortunately,
these
tools
not
yet
reached
state
maturity
because
complexity
process
aggravated
high
heterogeneity
that
easily
recapitulated
experimentally.
In
fact,
extensive
research
has
performed
preclinical
trials
carried
out
provided
sometimes
contradictory
results,
functionality
function
still
fully
understood.
study,
we
combined
tissue
clarification,
advanced
microscopy
image
analysis
develop
one-dimensional
computational
model
microvasculature
hemodynamics
inside
mouse
brain.
This
can
provide
information
about
flow
regime,
pressure
field
wall
shear
stress
among
other
fluid
dynamics
variables
Although
it
simplified
cerebral
microvasculature,
allows
insight
into
offers
several
additional
possibilities
systematically
microcirculatory
processes.
Royal Society Open Science,
Journal Year:
2025,
Volume and Issue:
12(1)
Published: Jan. 1, 2025
The
flow
network
model
is
an
established
approach
to
approximate
pressure–flow
relationships
in
a
bifurcating
network,
and
has
been
widely
used
many
contexts.
Existing
models
typically
assume
unidirectional
exploit
Poiseuille’s
law,
thus
neglect
the
impact
of
bifurcation
geometry
finite-sized
objects
on
flow.
We
determine
by
computing
Stokes
flows
two-dimensional
(2D)
using
Lightning-AAA
Rational
algorithm,
novel
mesh-free
algorithm
for
solving
2D
problems
utilizing
applied
complex
analysis
based
rational
approximation
Goursat
functions.
compute
conductances
bifurcations
with
different
channel
widths,
angles,
curved
boundary
geometries
fixed
circular
objects.
quantify
difference
between
computed
their
Poiseuille
law
approximations
demonstrate
importance
incorporating
detailed
into
existing
models.
parametrize
as
functions
dimensionless
parameters
object
machine
learning
approach,
which
simple
use
provides
more
accurate
than
law.
Finally,
details
are
presented.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: Dec. 15, 2021
Abstract
Blood
microcirculation
supplies
neurons
with
oxygen
and
nutrients,
contributes
to
clearing
their
neurotoxic
waste,
through
a
dense
capillary
network
connected
larger
tree-like
vessels.
This
complex
microvascular
architecture
results
in
highly
heterogeneous
blood
flow
travel
time
distributions,
whose
origin
consequences
on
brain
pathophysiology
are
poorly
understood.
Here,
we
analyze
highly-resolved
intracortical
transport
simulations
establish
the
physical
laws
governing
macroscopic
properties
micro-circulation.
We
show
that
network-driven
anomalous
leads
emergence
of
critical
regions,
whether
hypoxic
or
high
concentrations
amyloid-
β
,
waste
product
centrally
involved
Alzheimer’s
Disease.
develop
Continuous-Time
Random
Walk
theory
capturing
these
dynamics
predicting
such
regions
appear
much
earlier
than
anticipated
by
current
empirical
models
under
mild
hypoperfusion.
These
findings
provide
framework
for
understanding
modelling
impact
dysfunction
diseases,
including
Microcirculation,
Journal Year:
2021,
Volume and Issue:
28(5)
Published: Feb. 22, 2021
Recent
advancements
in
multiphoton
imaging
and
vascular
reconstruction
algorithms
have
increased
the
amount
of
data
on
cerebrovascular
circulation
for
statistical
analysis
hemodynamic
simulations.
Experimental
observations
offer
fundamental
insights
into
capillary
network
topology
but
mainly
within
a
narrow
field
view
typically
spanning
small
fraction
cortical
surface
(less
than
2%).
In
contrast,
larger-resolution
modalities,
such
as
computed
tomography
(CT)
or
magnetic
resonance
(MRI),
whole-brain
coverage
capture
only
larger
blood
vessels,
overlooking
microscopic
bed.
To
integrate
acquired
at
multiple
length
scales
with
different
neuroimaging
modalities
to
reconcile
brain-wide
macroscale
information
microscale
data,
we
developed
method
synthesizing
hemodynamically
equivalent
networks
entire
cerebral
circulation.
This
computational
approach
is
intended
aid
quantification
patterns
flow
metabolism
brain.
part
I,
described
mathematical
framework
image-guided
generation
synthetic
covering
large
arteries
from
circle
Willis
through
pial
leading
back
venous
sinuses.
Here
II,
introduce
novel
procedures
creating
microcirculatory
closure
that
mimics
realistic
We
demonstrate
our
capability
synthesize
whose
morphometrics
match
empirical
graphs
three
independent
state-of-the-art
laboratories
using
image
acquisition
protocols.
also
successfully
synthesized
twelve
complete
mouse
brain
hemisphere
suitable
performing
Synthetic
arterial
microvascular
allow
predictions.
Simulations
across
all
will
potentially
illuminate
organ-wide
supply
metabolic
functions
are
inaccessible
models
reconstructed
limited
spatial
coverage.
PLoS Computational Biology,
Journal Year:
2022,
Volume and Issue:
18(8), P. e1010166 - e1010166
Published: Aug. 5, 2022
The
microvasculature
plays
a
key
role
in
oxygen
transport
the
mammalian
brain.
Despite
close
coupling
between
cerebral
vascular
geometry
and
local
demand,
recent
experiments
have
reported
that
microvascular
occlusions
can
lead
to
unexpected
distant
tissue
hypoxia
infarction.
To
better
understand
spatial
correlation
hypoxic
regions
occlusion
sites,
we
used
both
vivo
silico
simulations
investigate
effects
of
penetrating
arteriole
trees
on
hypoxia.
In
rat
model
microembolisation,
25
μm
microspheres
were
injected
through
carotid
artery
occlude
arterioles.
representative
models
human
cortical
columns,
arterioles
occluded
by
simulating
same
size
was
simulated
using
Green’s
function
method.
locations
segmented,
two
novel
distance
analyses
implemented
study
their
correlation.
found
be
present
simulations,
mainly
due
hypoperfusion
region
downstream
site.
Furthermore,
reasonable
agreement
for
sites
is
shown
which
indicates
good
applicability
understanding
response
blood
flow
microemboli.
Neuroinformatics,
Journal Year:
2024,
Volume and Issue:
22(4), P. 679 - 706
Published: Sept. 23, 2024
Abstract
Advances
in
the
spatiotemporal
resolution
and
field-of-view
of
neuroimaging
tools
are
driving
mesoscale
studies
for
translational
neuroscience.
On
October
10,
2023,
Center
Mesoscale
Mapping
(CMM)
at
Massachusetts
General
Hospital
(MGH)
Athinoula
A.
Martinos
Biomedical
Imaging
Institute
Technology
(MIT)
Health
Sciences
based
Neuroimaging
Training
Program
(NTP)
hosted
a
symposium
exploring
state-of-the-art
this
rapidly
growing
area
research.
“Mesoscale
Brain
Mapping:
Bridging
Scales
Modalities
Neuroimaging”
brought
together
researchers
who
use
broad
range
imaging
techniques
to
study
brain
structure
function
convergence
microscopic
macroscopic
scales.
The
day-long
event
centered
on
areas
which
CMM
has
established
expertise,
including
development
emerging
technologies
their
application
clinical
needs
basic
neuroscience
questions.
in-person
welcomed
more
than
150
attendees,
57
faculty
members,
61
postdoctoral
fellows,
35
students,
four
industry
professionals,
represented
institutions
local,
regional,
international
levels.
also
served
training
goals
both
NTP.
content,
organization,
format
were
planned
collaboratively
by
trainees.
Many
presented
or
participated
panel
discussion,
thus
contributing
dissemination
they
have
developed
under
auspices
findings
obtained
using
those
technologies.
NTP
trainees
benefited
from
included
helped
organize
and/or
posters
gave
“flash”
oral
presentations.
In
addition
gaining
experience
presenting
work,
had
opportunities
throughout
day
engage
one-on-one
discussions
with
visiting
scientists
other
faculty,
potentially
opening
door
future
collaborations.
presentations
provided
deep
exploration
many
technological
advances
enabling
progress
structural
functional
imaging.
Finally,
students
worked
closely
develop
report
summarizing
content
putting
it
broader
context
current
state
field
share
scientific
community.
We
note
that
references
cited
here
include
conference
abstracts
corresponding
poster
Journal of Cerebral Blood Flow & Metabolism,
Journal Year:
2023,
Volume and Issue:
43(10), P. 1713 - 1725
Published: Jan. 17, 2023
Microvascular
stalling,
the
process
occurring
when
a
capillary
temporarily
loses
perfusion,
has
gained
increasing
interest
in
recent
years
through
its
demonstrated
presence
various
neuropathologies.
Studying
impact
of
such
stalls
on
surrounding
brain
tissue
is
paramount
importance
to
understand
their
role
diseases.
Despite
efforts
trying
study
stalling
events,
investigations
are
hampered
by
elusiveness
and
scarcity.
In
an
attempt
alleviate
these
hurdles,
we
present
here
novel
methodology
enabling
transient
occlusions
targeted
microvascular
segments
multiphoton
excitation
Rose
Bengal,
established
photothrombotic
agent.
With
n
=
7
mice
C57BL/6
J
(5
males
2
females)
95
photothrombosis
trials,
demonstrate
ability
triggering
reversible
blockages
illuminating
segment
during
∼300
s
at
1000
nm,
using
standard
Ti:Sapphire
femtosecond
laser.
Furthermore,
performed
concurrent
Optical
Coherence
Microscopy
(OCM)
angiography
imaging
network
highlight
specificity
occlusion
duration.
Through
comparison
with
control
group,
conclude
that
blood
flow
cessation
indeed
created
agent
via
temporary,
followed
recovery
less
than
24
h.
Moreover,
Immunohistology
points
toward
mechanism
driven
adherence
neutrophil
vascular
lumen.
This
observation
seems
be
promoted
inflammation
locally
activation
Bengal.
International Journal for Numerical Methods in Biomedical Engineering,
Journal Year:
2023,
Volume and Issue:
39(8)
Published: May 28, 2023
Abstract
Oxygen
transfer
from
blood
vessels
to
cortical
brain
tissue
is
representative
of
a
class
problems
with
mixed‐domain
character.
Large‐scale
efficient
computation
oxygen
concentration
dependent
on
the
manner
in
which
tubular
network
coupled
mesh.
Models
explicitly
resolve
interface
between
and
vasculature
contiguous
mesh
are
prohibitively
expensive
for
very
dense
cerebral
microvasculature.
We
propose
mesh‐free
technique
whereby
vascular
anatomical
(VAN)
represented
as
thin
directed
graph
serves
convection
oxygen,
surrounding
extravascular
Cartesian
grid
3D
voxels
throughout
transported
by
diffusion.
split
meshes
Schur
complement
method
domain
decomposition
obtain
reduced
set
system
equations
at
steady
state.
The
use
allows
corresponding
matrix
equation
be
solved
approximately
fast
Fourier
transform‐based
Poisson
solver,
an
effective
preconditioner
Krylov
subspace
iteration.
performance
this
enables
steady‐state
simulation
perfusion
anatomically
accurate
networks
down
single
micron
resolution
without
need
supercomputers.
Applied Mathematical Modelling,
Journal Year:
2023,
Volume and Issue:
123, P. 213 - 240
Published: July 3, 2023
Models
of
the
micro-circulatory
blood
flow
in
brain
can
play
a
key
role
understanding
variety
cerebrovascular
diseases
that
occur
microvasculature.
These
conditions
are
often
linked
to
structural
modifications
vessel
network,
alterations
patterns,
as
well
impairment
autoregulatory
response,
all
which
pathological
changes
model
should
be
able
address
if
it
were
have
any
clinical
value.
Furthermore,
results
validated
against
MRI
data,
simulations
need
computationally
feasible
when
used
on
networks
scale
an
voxel.
This
requires
some
form
upscaling
approach
bypasses
for
explicit
architectural
representation
whole
network
while
maintaining
relevant
anatomical
connections.
To
this
end,
we
developed
hybrid
multiscale
and
autoregulation
traces
dynamic
flow,
volume,
pressure
cortical
microvasculature,
where
discrete
topology
penetrating
vessels
is
preserved,
these
then
appropriately
coupled
homogenised
capillary
bed
by
spatially
distributing
support
function
terminal
endings.
In
contrast
other
models,
here
accounts
physiological
phenomena
processes
microvessels.
We
show
how
adaptive
meshing
scheme
study
employed
ensure
scale-invariant
coupling
formulation
numerically
accurate
simulations,
without
compromising
computational
feasibility
model.
A
statistically
voxel
generated,
parameter
values
calibrated
using
Monte
Carlo
Filtering
analysis
physiologically
informed.
The
found
capture
steep
gradients
been
reported
at
interfaces.
response
upstream
drop,
recover
cerebral
exhibiting
characteristic
behaviour
terms
calibre
biphasic
response.
Overall,
offers
high-quality
characterisation
microvasculature
improved
efficiency
lays
ground
whole-brain
simulations.