<s>
CUBIC	B-Algorithm
(	O
abbreviation	O
for	O
“	O
clear	O
,	O
unobstructed	O
brain/body	O
imaging	O
cocktails	O
and	O
computational	O
analysis	O
)	O
is	O
a	O
histology	O
method	O
that	O
allows	O
tissues	O
to	O
be	O
transparent	O
(	O
process	O
called	O
“	O
tissue	O
clearing	O
”	O
)	O
.	O
</s>
<s>
But	O
in	O
upcoming	O
years	O
there	O
were	O
other	O
works	O
published	O
,	O
using	O
CUBIC	B-Algorithm
method	O
on	O
other	O
tissues	O
like	O
lymph	O
nodes	O
or	O
mammary	O
glands	O
.	O
</s>
<s>
CUBIC	B-Algorithm
can	O
be	O
also	O
combined	O
with	O
CLARITY-based	O
tissue	O
clearing	O
methods	O
.	O
</s>
<s>
Development	O
of	O
CUBIC	B-Algorithm
pipeline	O
was	O
inspired	O
by	O
previously	O
published	O
clearing	O
protocol	O
named	O
Scale	O
(	O
mixture	O
of	O
glycerol	O
,	O
urea	O
and	O
detergent	O
)	O
,	O
because	O
of	O
its	O
simplicity	O
and	O
optimal	O
compatibility	O
with	O
fluorescent	O
proteins	O
.	O
</s>
<s>
Authors	O
of	O
CUBIC	B-Algorithm
screened	O
40	O
chemicals	O
corresponding	O
to	O
those	O
used	O
in	O
Scale	O
with	O
aim	O
to	O
conserve	O
compatibility	O
with	O
fluorescent	O
reporters	O
but	O
achieve	O
better	O
and	O
faster	O
clearing	O
of	O
the	O
tissue	O
.	O
</s>
<s>
First	O
solution	O
,	O
referred	O
as	O
ScaleCUBIC-1	O
,	O
CUBIC-1	O
or	O
just	O
reagent-1	O
,	O
is	O
composed	O
of	O
N	O
,	O
N	O
,	O
N’	O
,	O
N’-tetrakis( 2-hydroxypropyl	O
)	O
ethylenediamine	O
(	O
commercially	O
under	O
name	O
Quadrol	O
)	O
,	O
urea	O
and	O
Triton	O
X-100	O
in	O
water	O
.	O
</s>
<s>
Second	O
solution	O
,	O
referred	O
as	O
ScaleCUBIC-2	O
,	O
CUBIC-2	O
or	O
just	O
reagent-2	O
,	O
is	O
composed	O
of	O
urea	O
and	O
sucrose	O
in	O
water	O
.	O
</s>
<s>
The	O
CUBIC	B-Algorithm
protocol	O
can	O
be	O
also	O
combined	O
with	O
perfusion	O
and	O
provide	O
whole	O
organ	O
and	O
whole	O
body	O
clearing	O
of	O
rodents	O
.	O
</s>
<s>
Besides	O
its	O
use	O
as	O
standalone	O
protocol	O
for	O
clearing	O
,	O
CUBIC-based	O
composition	O
of	O
reagents	O
can	O
be	O
used	O
as	O
refractive	O
index	O
matching	O
solution	O
for	O
CLARITY	B-Algorithm
.	O
</s>
<s>
This	O
than	O
improve	O
clearing	O
abilities	O
of	O
CLARITY	B-Algorithm
on	O
tissues	O
which	O
stay	O
opaque	O
because	O
of	O
their	O
pigmentation	O
by	O
hemoglobin	O
.	O
</s>
<s>
The	O
improvement	O
of	O
CUBIC	B-Algorithm
reagents	O
has	O
progressed	O
and	O
been	O
reported	O
.	O
</s>
<s>
The	O
CUBIC	B-Algorithm
method	O
is	O
very	O
powerful	O
,	O
due	O
to	O
amino	O
alcohols	O
and	O
consequent	O
ability	O
to	O
clear	O
almost	O
any	O
organ	O
or	O
even	O
whole	O
body	O
of	O
mice	O
.	O
</s>
<s>
Despite	O
organic	O
solvents	O
,	O
reagents	O
used	O
in	O
CUBIC	B-Algorithm
are	O
not	O
toxic	O
or	O
aggressive	O
to	O
optics	O
of	O
microscopes	O
,	O
on	O
the	O
other	O
hand	O
the	O
handling	O
with	O
them	O
can	O
be	O
also	O
tricky	O
due	O
to	O
their	O
high	O
viscosity	B-Application
.	O
</s>
<s>
Also	O
,	O
in	O
comparison	O
with	O
solvent	O
based	O
methods	O
like	O
3DISCO	O
the	O
CUBIC	B-Algorithm
as	O
method	O
based	O
on	O
simple	O
diffusion	O
is	O
still	O
take	O
slightly	O
longer	O
times	O
for	O
clearing	O
same	O
tissue	O
.	O
</s>
<s>
Because	O
of	O
high	O
concentration	O
of	O
detergent	O
,	O
the	O
CUBIC	B-Algorithm
ca	O
also	O
partially	O
diminishes	O
the	O
fluorescence	O
or	O
disturb	O
ultrastructure	O
of	O
the	O
tissue	O
.	O
</s>
<s>
CUBIC	B-Algorithm
was	O
optimized	O
and	O
used	O
for	O
wide	O
spread	O
of	O
applications	O
and	O
tissues	O
.	O
</s>
<s>
CUBIC	B-Algorithm
was	O
also	O
modified	O
and	O
used	O
for	O
clearing	O
of	O
chicken	O
embryos	O
or	O
marmoset	O
brains	O
.	O
</s>
<s>
In	O
recent	O
study	O
was	O
also	O
shown	O
few	O
variants	O
of	O
basic	O
CUBIC	B-Algorithm
pipeline	O
,	O
in	O
this	O
case	O
used	O
for	O
diagnostic	O
of	O
human	O
pathologies	O
both	O
on	O
native	O
and	O
formalin	O
fixed	O
paraffin	O
embedded	O
tissues	O
.	O
</s>
