<s>
A	O
specific	O
branch	O
of	O
contrast-enhanced	O
ultrasound	B-Application
,	O
acoustic	B-Algorithm
angiography	I-Algorithm
is	O
a	O
minimally	O
invasive	O
and	O
non-ionizing	O
medical	B-Application
imaging	I-Application
technique	I-Application
used	O
to	O
visualize	O
vasculature	O
.	O
</s>
<s>
Acoustic	B-Algorithm
angiography	I-Algorithm
was	O
first	O
developed	O
by	O
the	O
Dayton	O
Laboratory	O
at	O
North	O
Carolina	O
State	O
University	O
and	O
provides	O
a	O
safe	O
,	O
portable	O
,	O
and	O
inexpensive	O
alternative	O
to	O
the	O
most	O
common	O
methods	O
of	O
angiography	O
such	O
as	O
Magnetic	B-Algorithm
Resonance	I-Algorithm
Angiography	I-Algorithm
and	O
Computed	O
Tomography	O
Angiography	O
.	O
</s>
<s>
Although	O
ultrasound	B-Application
does	O
not	O
traditionally	O
exhibit	O
the	O
high	O
resolution	O
of	O
MRI	B-Algorithm
or	O
CT	O
,	O
high-frequency	O
ultrasound	B-Application
(	O
HFU	O
)	O
achieves	O
relatively	O
high	O
resolution	O
by	O
sacrificing	O
some	O
penetration	O
depth	O
.	O
</s>
<s>
Acoustic	B-Algorithm
angiography	I-Algorithm
overcomes	O
the	O
weaknesses	O
of	O
HFU	O
by	O
combining	O
contrast-enhanced	O
ultrasound	B-Application
with	O
the	O
use	O
of	O
a	O
dual-element	O
ultrasound	B-Algorithm
transducer	I-Algorithm
to	O
achieve	O
high	O
resolution	O
visualization	O
of	O
blood	O
vessels	O
at	O
relatively	O
deep	O
penetration	O
levels	O
.	O
</s>
<s>
Acoustic	B-Algorithm
angiography	I-Algorithm
is	O
performed	O
by	O
first	O
injecting	O
specially	O
designed	O
microbubbles	O
with	O
a	O
low	O
resonant	B-Application
frequency	I-Application
into	O
the	O
vessels	O
.	O
</s>
<s>
Next	O
,	O
a	O
low-frequency	O
transducer	O
element	O
with	O
good	O
depth	O
penetration	O
is	O
used	O
to	O
send	O
ultrasound	B-Application
waves	O
into	O
the	O
sample	O
at	O
the	O
resonant	B-Application
frequency	I-Application
of	O
the	O
microbubbles	O
.	O
</s>
<s>
Currently	O
,	O
the	O
most	O
common	O
techniques	O
used	O
for	O
angiography	O
are	O
X-ray	B-Library
CT	O
and	O
MRI	B-Algorithm
.	O
</s>
<s>
However	O
,	O
many	O
other	O
methods	O
are	O
used	O
for	O
performing	O
angiography	O
in	O
special	O
circumstances	O
,	O
such	O
as	O
the	O
use	O
of	O
optical	B-Application
coherence	I-Application
tomography	I-Application
for	O
performing	O
angiography	O
during	O
retinal	O
exams	O
.	O
</s>
<s>
MRI	B-Algorithm
angiography	O
provides	O
the	O
highest	O
resolution	O
of	O
the	O
current	O
angiographic	O
methods	O
and	O
can	O
often	O
be	O
performed	O
without	O
the	O
use	O
of	O
contrast	O
agents	O
by	O
modifying	O
the	O
pulse	O
sequence	O
to	O
visualize	O
aspects	O
of	O
the	O
vessels	O
such	O
as	O
blood	O
flow	O
.	O
</s>
<s>
On	O
the	O
other	O
hand	O
,	O
x-ray	B-Library
CT	O
angiography	O
requires	O
the	O
use	O
of	O
a	O
contrast	O
agent	O
,	O
but	O
still	O
maintains	O
relatively	O
high	O
resolution	O
.	O
</s>
<s>
Both	O
are	O
relatively	O
slow	O
and	O
require	O
expensive	O
equipment	O
,	O
while	O
x-ray	B-Library
CT	O
also	O
exposes	O
patients	O
to	O
potentially	O
harmful	O
ionizing	O
radiation	O
.	O
</s>
<s>
Acoustic	B-Algorithm
angiography	I-Algorithm
is	O
able	O
to	O
fill	O
this	O
need	O
.	O
</s>
<s>
By	O
using	O
microbubbles	O
as	O
a	O
contrast	O
agent	O
and	O
a	O
dual-element	B-Algorithm
transducer	I-Algorithm
for	O
signal	O
identification	O
,	O
acoustic	B-Algorithm
angiography	I-Algorithm
achieves	O
depth	O
,	O
vessel	O
contrast	O
,	O
and	O
resolution	O
not	O
possible	O
with	O
other	O
ultrasound	B-Application
techniques	O
.	O
</s>
<s>
Ultrasound	B-Application
contrast	O
agents	O
are	O
particles	O
used	O
in	O
ultrasound	B-Application
scans	I-Application
to	O
improve	O
image	O
contrast	O
.	O
</s>
<s>
The	O
first	O
reported	O
use	O
of	O
an	O
ultrasound	B-Application
contrast	O
agent	O
was	O
by	O
Dr.	O
Raymond	O
Gramiak	O
and	O
Pravin	O
Shah	O
in	O
1968	O
,	O
when	O
they	O
injected	O
saline	O
into	O
the	O
aortic	O
root	O
of	O
the	O
heart	O
and	O
observed	O
increased	O
contrast	O
.	O
</s>
<s>
Although	O
most	O
ultrasound	B-Application
contrast	O
agents	O
take	O
the	O
form	O
of	O
microbubbles	O
,	O
other	O
types	O
exist	O
,	O
such	O
as	O
perfluorocarbon	O
nanoparticles	O
or	O
echogenic	O
liposomes	O
.	O
</s>
<s>
Microbubbles	O
work	O
as	O
contrast	O
agents	O
in	O
ultrasound	B-Application
for	O
two	O
main	O
reasons	O
:	O
The	O
large	O
difference	O
in	O
acoustic	O
impedance	O
between	O
body	O
tissues	O
and	O
the	O
microbubbles	O
and	O
their	O
quality	O
of	O
having	O
a	O
resonant	B-Application
frequency	I-Application
generally	O
under	O
10MHz	O
.	O
</s>
<s>
Due	O
to	O
the	O
larger	O
mismatch	O
in	O
acoustic	O
impedances	O
,	O
the	O
microbubbles	O
are	O
near-perfect	O
reflectors	O
of	O
ultrasound	B-Application
waves	O
in	O
the	O
body	O
.	O
</s>
<s>
Furthermore	O
,	O
at	O
their	O
resonant	B-Application
frequency	I-Application
,	O
the	O
microbubbles	O
have	O
a	O
relatively	O
large-magnitude	O
broadband	O
frequency	O
response	O
,	O
which	O
is	O
picked	O
up	O
by	O
the	O
ultrasound	B-Algorithm
transducer	I-Algorithm
.	O
</s>
<s>
In	O
classical	O
contrast-enhanced	O
ultrasound	B-Application
,	O
many	O
methods	O
exist	O
for	O
separating	O
signal	O
reflected	O
by	O
the	O
microbubbles	O
and	O
signal	O
reflected	O
by	O
surrounding	O
body	O
tissues	O
.	O
</s>
<s>
Most	O
of	O
these	O
methods	O
utilize	O
the	O
subharmonic	O
and	O
super	O
harmonic	O
response	O
of	O
the	O
microbubbles	O
,	O
as	O
well	O
as	O
the	O
microbubbles	O
nonlinear	O
response	O
to	O
ultrasound	B-Application
waves	O
,	O
as	O
opposed	O
to	O
body	O
tissues	O
linear	O
response	O
to	O
ultrasound	B-Application
waves	O
.	O
</s>
<s>
Some	O
of	O
the	O
more	O
common	O
filtering	B-Architecture
methods	O
are	O
listed	O
below	O
.	O
</s>
<s>
Subharmonic	O
filtering	B-Architecture
:	O
This	O
works	O
by	O
filtering	B-Architecture
out	O
all	O
signals	O
but	O
the	O
subharmonic	O
signals	O
.	O
</s>
<s>
However	O
,	O
since	O
this	O
filters	O
for	O
the	O
low-frequency	O
signals	O
,	O
the	O
resolution	O
is	O
slightly	O
degraded	O
as	O
spatial	O
resolution	O
in	O
ultrasound	B-Application
is	O
dependent	O
on	O
the	O
acoustic	O
frequency	O
.	O
</s>
<s>
Super	O
harmonic	O
filtering	B-Architecture
:	O
Similar	O
to	O
subharmonic	O
filtering	B-Architecture
,	O
this	O
works	O
by	O
filtering	B-Architecture
all	O
but	O
the	O
super	O
harmonic	O
frequencies	O
,	O
which	O
are	O
mostly	O
emitted	O
by	O
the	O
microbubbles	O
and	O
not	O
surrounding	O
tissue	O
.	O
</s>
<s>
Unlike	O
subharmonic	O
filtering	B-Architecture
,	O
the	O
resolution	O
is	O
actually	O
improved	O
since	O
only	O
the	O
high-frequency	O
response	O
is	O
received	O
.	O
</s>
<s>
Phase	O
inversion	O
:	O
This	O
filtering	B-Architecture
method	O
utilizes	O
the	O
characteristically	O
nonlinear	O
response	O
of	O
the	O
microbubbles	O
to	O
ultrasound	B-Application
waves	O
.	O
</s>
<s>
With	O
the	O
creation	O
of	O
a	O
dual-element	B-Algorithm
transducer	I-Algorithm
,	O
these	O
filtering	B-Architecture
methods	O
are	O
no	O
longer	O
critical	O
.	O
</s>
<s>
This	O
is	O
what	O
distinguishes	O
acoustic	B-Algorithm
angiography	I-Algorithm
from	O
the	O
more	O
generic	O
contrast-enhanced	O
ultrasound	B-Application
.	O
</s>
<s>
An	O
element	O
centered	O
at	O
a	O
low	O
frequency	O
serves	O
to	O
excite	O
the	O
microbubbles	O
at	O
their	O
resonant	B-Application
frequency	I-Application
,	O
while	O
an	O
element	O
centered	O
at	O
a	O
high	O
frequency	O
receives	O
the	O
super	O
harmonic	O
response	O
of	O
the	O
microbubbles	O
.	O
</s>
<s>
Since	O
the	O
tissue	O
is	O
excited	O
by	O
the	O
low	O
frequency	O
input	O
and	O
does	O
not	O
produce	O
a	O
high	O
frequency	O
response	O
,	O
the	O
only	O
response	O
received	O
by	O
the	O
dual-element	B-Algorithm
transducer	I-Algorithm
is	O
that	O
originating	O
from	O
the	O
microbubbles	O
.	O
</s>
<s>
Generally	O
,	O
PVDF	O
is	O
not	O
a	O
good	O
choice	O
for	O
an	O
ultrasound	B-Algorithm
transducer	I-Algorithm
because	O
it	O
has	O
a	O
relatively	O
poor	O
transmitting	O
constant	O
,	O
however	O
,	O
since	O
acoustic	B-Algorithm
angiography	I-Algorithm
separates	O
the	O
transmitting	O
and	O
receiving	O
elements	O
,	O
this	O
is	O
no	O
longer	O
an	O
issue	O
.	O
</s>
<s>
As	O
acoustic	B-Algorithm
angiography	I-Algorithm
uses	O
a	O
dual-element	O
ultrasonic	B-Algorithm
transducer	I-Algorithm
in	O
the	O
format	O
of	O
a	O
focused	O
ultrasound	B-Algorithm
probe	I-Algorithm
,	O
it	O
is	O
not	O
feasible	O
to	O
form	O
an	O
array	O
of	O
transducers	O
as	O
can	O
be	O
done	O
in	O
other	O
forms	O
of	O
ultrasound	B-Application
imagining	I-Application
.	O
</s>
<s>
Thus	O
acoustic	B-Algorithm
angiography	I-Algorithm
images	O
are	O
formed	O
by	O
combining	O
multiple	O
a-mode	O
images	O
where	O
each	O
a-mode	O
is	O
a	O
one-dimensional	O
image	O
identifying	O
the	O
acoustic	O
boundaries	O
along	O
a	O
vector	O
originating	O
at	O
the	O
transducer	O
.	O
</s>
<s>
In	O
the	O
linear	O
sweep	O
configuration	O
,	O
the	O
ultrasound	B-Algorithm
probe	I-Algorithm
is	O
mechanically	O
moved	O
,	O
either	O
by	O
an	O
external	O
mechanism	O
or	O
hand	O
,	O
in	O
a	O
direction	O
orthogonal	O
to	O
the	O
direction	O
of	O
the	O
a-scan	O
.	O
</s>
<s>
Once	O
data	O
has	O
been	O
collected	O
as	O
described	O
above	O
,	O
it	O
can	O
be	O
processed	O
to	O
form	O
a	O
variety	O
of	O
image	O
types	O
including	O
projections	B-Algorithm
and	O
volumetric	O
reconstruction	O
.	O
</s>
<s>
Projection	B-Algorithm
images	O
in	O
ultrasound	B-Application
are	O
similar	O
in	O
concept	O
to	O
projection	B-Algorithm
radiography	O
.	O
</s>
<s>
However	O
,	O
instead	O
of	O
projecting	O
the	O
degree	O
of	O
absorbance	O
of	O
X-ray	B-Library
photons	I-Library
along	O
a	O
given	O
path	O
,	O
projection	B-Algorithm
images	O
in	O
ultrasound	B-Application
generally	O
project	O
the	O
mismatch	O
of	O
acoustic	O
impedance	O
and	O
the	O
location	O
along	O
a	O
given	O
boundary	O
in	O
tissue	O
.	O
</s>
<s>
The	O
maximum	O
amplitude	O
projection	B-Algorithm
or	O
the	O
maximum	B-Application
intensity	I-Application
projection	I-Application
is	O
an	O
image	O
processing	O
technique	O
used	O
to	O
project	O
three	O
dimensional	O
data	O
onto	O
a	O
two	O
dimensional	O
image	O
.	O
</s>
<s>
In	O
many	O
forms	O
of	O
ultrasound	B-Application
imaging	I-Application
and	O
photoacoustic	B-Algorithm
imaging	I-Algorithm
,	O
the	O
maximum	O
amplitude	O
of	O
the	O
signal	O
along	O
a	O
given	O
a-scan	O
is	O
used	O
as	O
the	O
value	O
for	O
a	O
pixel	O
associated	O
with	O
that	O
a-scan	O
.	O
</s>
<s>
This	O
simple	O
image	O
reconstruction	O
technique	O
allows	O
for	O
easily	O
formed	O
and	O
interpretable	O
projection	B-Algorithm
images	O
formed	O
from	O
acoustic	O
signals	O
.	O
</s>
<s>
Volumetric	O
renderings	O
convert	O
volumetric	O
data	O
into	O
projection	B-Algorithm
images	O
.	O
</s>
<s>
Most	O
methods	O
use	O
data	O
acquired	O
in	O
lower	O
dimensions	O
to	O
generate	O
voxels	B-Algorithm
,	O
volumetric	O
pixels	O
,	O
that	O
can	O
form	O
3D	O
images	O
when	O
combined	O
.	O
</s>
<s>
Common	O
volume	O
reconstruction	O
techniques	O
include	O
pixel-nearest-neighbors	O
,	O
voxel-nearest-neighbors	O
,	O
distance-weighted	O
voxels	B-Algorithm
,	O
and	O
function	O
based	O
methods	O
used	O
to	O
statistically	O
infer	O
the	O
value	O
of	O
a	O
given	O
voxel	B-Algorithm
.	O
</s>
<s>
As	O
acoustic	B-Algorithm
angiography	I-Algorithm
is	O
currently	O
under	O
development	O
,	O
this	O
specific	O
branch	O
of	O
contrast-enhanced	O
ultrasound	B-Application
is	O
not	O
currently	O
used	O
in	O
clinical	O
settings	O
.	O
</s>
<s>
The	O
majority	O
of	O
the	O
previous	O
work	O
using	O
acoustic	B-Algorithm
angiography	I-Algorithm
has	O
studied	O
angiogenesis	O
in	O
animal	O
models	O
for	O
research	O
purposes	O
.	O
</s>
<s>
Though	O
the	O
FDA	O
has	O
only	O
approved	O
contrast-enhanced	O
ultrasound	B-Application
use	O
in	O
one	O
clinical	O
application	O
in	O
the	O
United	O
States	O
,	O
echocardiography	B-Application
,	O
the	O
broader	O
technique	O
has	O
been	O
used	O
throughout	O
Europe	O
and	O
Asia	O
to	O
great	O
success	O
in	O
a	O
variety	O
of	O
clinical	O
applications	O
.	O
</s>
<s>
To	O
learn	O
more	O
,	O
see	O
the	O
current	O
applications	O
of	O
contrast	O
enhanced	O
ultrasound	B-Application
.	O
</s>
<s>
The	O
only	O
use	O
of	O
acoustic	B-Algorithm
angiography	I-Algorithm
that	O
has	O
been	O
investigated	O
in	O
clinical	O
settings	O
to	O
date	O
studied	O
angiogenesis	O
in	O
the	O
peripheral	O
vasculature	O
of	O
human	O
breast	O
tissue	O
.	O
</s>
<s>
This	O
study	O
investigated	O
if	O
acoustic	B-Algorithm
angiography	I-Algorithm
could	O
be	O
used	O
to	O
reduce	O
the	O
need	O
for	O
biopsy	O
of	O
breast	O
tissue	O
when	O
diagnosing	O
if	O
lesions	O
in	O
breast	O
tissue	O
were	O
cancerous	O
or	O
not	O
.	O
</s>
<s>
Using	O
acoustic	B-Algorithm
angiography	I-Algorithm
,	O
the	O
authors	O
collected	O
and	O
reconstructed	O
the	O
3D	O
volumes	O
associated	O
with	O
vasculature	O
surrounding	O
lesions	O
in	O
the	O
breast	O
.	O
</s>
