<s>
MRI	B-Algorithm
contrast	I-Algorithm
agents	I-Algorithm
are	O
contrast	B-Algorithm
agents	I-Algorithm
used	O
to	O
improve	O
the	O
visibility	O
of	O
internal	O
body	O
structures	O
in	O
magnetic	O
resonance	O
imaging	O
(	O
MRI	O
)	O
.	O
</s>
<s>
The	O
most	O
commonly	O
used	O
compounds	O
for	O
contrast	B-Algorithm
enhancement	I-Algorithm
are	O
gadolinium-based	O
contrast	B-Algorithm
agents	I-Algorithm
(	O
GBCAs	O
)	O
.	O
</s>
<s>
Such	O
MRI	B-Algorithm
contrast	I-Algorithm
agents	I-Algorithm
shorten	O
the	O
relaxation	B-Algorithm
times	I-Algorithm
of	O
nuclei	O
within	O
body	O
tissues	O
following	O
oral	O
or	O
intravenous	O
administration	O
.	O
</s>
<s>
Random	O
molecular	O
rotational	O
oscillations	O
matching	O
the	O
resonance	O
frequency	O
of	O
the	O
nuclear	O
spins	O
provide	O
the	O
"	O
relaxation	B-Algorithm
"	O
mechanisms	O
that	O
bring	O
the	O
net	O
magnetization	O
back	O
to	O
its	O
equilibrium	O
position	O
in	O
alignment	O
with	O
the	O
applied	O
magnetic	O
field	O
.	O
</s>
<s>
The	O
magnitude	O
of	O
the	O
spin	O
polarization	O
detected	O
by	O
the	O
receiver	O
is	O
used	O
to	O
form	O
the	O
MR	O
image	O
but	O
decays	O
with	O
a	O
characteristic	O
time	O
constant	O
known	O
as	O
the	O
T1	B-Algorithm
relaxation	I-Algorithm
time	I-Algorithm
.	O
</s>
<s>
Water	O
protons	O
in	O
different	O
tissues	O
have	O
different	O
T1	B-Algorithm
values	O
,	O
which	O
is	O
one	O
of	O
the	O
main	O
sources	O
of	O
contrast	O
in	O
MR	O
images	O
.	O
</s>
<s>
A	O
contrast	B-Algorithm
agent	I-Algorithm
usually	O
shortens	O
,	O
but	O
in	O
some	O
instances	O
increases	O
,	O
the	O
value	O
of	O
T1	B-Algorithm
of	O
nearby	O
water	O
protons	O
thereby	O
altering	O
the	O
contrast	O
in	O
the	O
image	O
.	O
</s>
<s>
Most	O
clinically	O
used	O
MRI	B-Algorithm
contrast	I-Algorithm
agents	I-Algorithm
work	O
by	O
shortening	O
the	O
T1	B-Algorithm
relaxation	I-Algorithm
time	I-Algorithm
of	O
protons	O
inside	O
tissues	O
via	O
interactions	O
with	O
the	O
nearby	O
contrast	B-Algorithm
agent	I-Algorithm
.	O
</s>
<s>
Thermally	O
driven	O
motion	O
of	O
the	O
strongly	O
paramagnetic	O
metal	O
ions	O
in	O
the	O
contrast	B-Algorithm
agent	I-Algorithm
generate	O
the	O
oscillating	O
magnetic	O
fields	O
that	O
provide	O
the	O
relaxation	B-Algorithm
mechanisms	O
that	O
enhance	O
the	O
rate	O
of	O
decay	O
of	O
the	O
induced	O
polarization	O
.	O
</s>
<s>
MRI	B-Algorithm
contrast	I-Algorithm
agents	I-Algorithm
may	O
be	O
administered	O
by	O
injection	O
into	O
the	O
blood	O
stream	O
or	O
orally	O
,	O
depending	O
on	O
the	O
subject	O
of	O
interest	O
.	O
</s>
<s>
MRI	B-Algorithm
contrast	I-Algorithm
agents	I-Algorithm
can	O
be	O
classified	O
by	O
their	O
:	O
</s>
<s>
Gadolinium(III )	O
containing	O
MRI	B-Algorithm
contrast	I-Algorithm
agents	I-Algorithm
(	O
often	O
termed	O
simply	O
"	O
gado	O
"	O
or	O
"	O
gad	O
"	O
)	O
are	O
the	O
most	O
commonly	O
used	O
for	O
enhancement	O
of	O
vessels	O
in	O
MR	B-Algorithm
angiography	I-Algorithm
or	O
for	O
brain	O
tumor	O
enhancement	O
associated	O
with	O
the	O
degradation	O
of	O
the	O
blood	O
–	O
brain	O
barrier	O
.	O
</s>
<s>
Available	O
Gadolinium-based	O
contrast	B-Algorithm
agents	I-Algorithm
(	O
GBCAs	O
)	O
(	O
brand	O
names	O
,	O
approved	O
for	O
human	O
use	O
by	O
EMA	O
and	O
by	O
the	O
FDA	O
in	O
1988	O
.	O
</s>
<s>
The	O
spectrum	O
of	O
adverse	O
drug	O
reactions	O
is	O
greater	O
with	O
GBCA	O
than	O
with	O
iodinated	O
contrast	B-Algorithm
agents	I-Algorithm
(	O
Radiocontrast	B-Application
agents	I-Application
)	O
.	O
</s>
<s>
NSF	O
can	O
be	O
caused	O
by	O
linear	O
and	O
macrocyclic	O
(	O
macrocyclic	O
ionic	O
compounds	O
have	O
been	O
found	O
the	O
least	O
likely	O
to	O
release	O
the	O
Gd3+	O
)	O
,	O
gadolinium-containing	O
MRI	B-Algorithm
contrast	I-Algorithm
agents	I-Algorithm
although	O
much	O
more	O
frequently	O
by	O
linear	O
.	O
</s>
<s>
The	O
FDA	O
has	O
asked	O
doctors	O
to	O
limit	O
the	O
use	O
of	O
Gadolinium	O
contrast	B-Algorithm
agents	I-Algorithm
to	O
examinations	O
where	O
necessary	O
information	O
is	O
obtained	O
only	O
through	O
its	O
use	O
.	O
</s>
<s>
Continuing	O
evidence	O
of	O
the	O
retention	O
of	O
gadolinium	O
in	O
brain	O
and	O
other	O
tissues	O
following	O
exposure	O
to	O
gadolinium	O
containing	O
contrast	B-Algorithm
media	I-Algorithm
,	O
has	O
led	O
to	O
a	O
safety	O
review	O
by	O
the	O
Committee	O
for	O
Medicinal	O
Products	O
for	O
Human	O
Use	O
(	O
CHMP	O
)	O
which	O
led	O
the	O
EMA	O
to	O
suspend	O
linear	O
gadolinium-based	O
media	O
,	O
in	O
which	O
Gd3+	O
has	O
a	O
lower	O
binding	O
affinity	O
,	O
in	O
2017	O
.	O
</s>
<s>
In	O
the	O
United	O
States	O
,	O
the	O
research	O
has	O
led	O
the	O
FDA	O
to	O
revise	O
its	O
class	O
warnings	O
for	O
all	O
gadolinium-based	O
contrast	B-Algorithm
media	I-Algorithm
.	O
</s>
<s>
The	O
World	O
Health	O
Organization	O
issued	O
a	O
restriction	O
on	O
use	O
of	O
several	O
gadolinium	O
contrast	B-Algorithm
agents	I-Algorithm
in	O
November	O
2009	O
stating	O
that	O
"	O
High-risk	O
gadolinium-containing	O
contrast	B-Algorithm
agents	I-Algorithm
(	O
Optimark	O
,	O
Omniscan	O
,	O
Magnevist	O
,	O
Magnegita	O
,	O
and	O
Gado-MRT	O
ratiopharm	O
)	O
are	O
contraindicated	O
in	O
patients	O
with	O
severe	O
kidney	O
problems	O
,	O
in	O
patients	O
who	O
are	O
scheduled	O
for	O
or	O
have	O
recently	O
received	O
a	O
liver	O
transplant	O
,	O
and	O
in	O
newborn	O
babies	O
up	O
to	O
four	O
weeks	O
of	O
age.	O
"	O
</s>
<s>
In	O
magnetic	O
resonance	O
imaging	O
in	O
pregnancy	O
,	O
gadolinium	O
contrast	B-Algorithm
agents	I-Algorithm
in	O
the	O
first	O
trimester	O
is	O
associated	O
with	O
a	O
slightly	O
increased	O
risk	O
of	O
a	O
childhood	O
diagnosis	O
of	O
several	O
forms	O
of	O
rheumatism	O
,	O
inflammatory	O
disorders	O
,	O
or	O
infiltrative	O
skin	O
conditions	O
,	O
according	O
to	O
a	O
retrospective	O
study	O
including	O
397	O
infants	O
prenatally	O
exposed	O
to	O
gadolinium	O
contrast	O
.	O
</s>
<s>
Two	O
types	O
of	O
iron	O
oxide	O
contrast	B-Algorithm
agents	I-Algorithm
exist	O
:	O
superparamagnetic	O
iron	O
oxide	O
(	O
SPIO	O
)	O
and	O
ultrasmall	O
superparamagnetic	O
iron	O
oxide	O
(	O
USPIO	O
)	O
.	O
</s>
<s>
These	O
contrast	B-Algorithm
agents	I-Algorithm
consist	O
of	O
suspended	O
colloids	O
of	O
iron	O
oxide	O
nanoparticles	O
and	O
when	O
injected	O
during	O
imaging	O
reduce	O
the	O
T2	O
signals	O
of	O
absorbing	O
tissues	O
.	O
</s>
<s>
SPIO	O
and	O
USPIO	O
contrast	B-Algorithm
agents	I-Algorithm
have	O
been	O
used	O
successfully	O
in	O
some	O
instances	O
for	O
liver	O
lesion	O
evaluation	O
.	O
</s>
<s>
Clariscan	B-Architecture
(	O
also	O
known	O
as	O
PEG-fero	O
,	O
Feruglose	O
,	O
and	O
NC100150	O
)	O
.	O
</s>
<s>
This	O
iron	O
based	O
contrast	B-Algorithm
agent	I-Algorithm
was	O
never	O
commercially	O
launched	O
and	O
its	O
development	O
was	O
discontinued	O
in	O
early	O
2000s	O
due	O
to	O
safety	O
concerns	O
.	O
</s>
<s>
In	O
2017	O
GE	O
Healthcare	O
launched	O
a	O
macrocyclic	O
extracellular	O
gadolinium	O
based	O
contrast	B-Algorithm
agent	I-Algorithm
containing	O
gadoteric	B-Architecture
acid	I-Architecture
as	O
gadoterate	B-Architecture
meglumine	I-Architecture
under	O
the	O
trade	O
name	O
Clariscan	B-Architecture
.	O
</s>
<s>
Superparamagnetic	B-Algorithm
iron	I-Algorithm
–	I-Algorithm
platinum	I-Algorithm
particles	I-Algorithm
(	O
SIPPs	B-Algorithm
)	O
have	O
been	O
reported	O
and	O
had	O
significantly	O
better	O
T2	O
relaxivities	O
compared	O
with	O
the	O
more	O
common	O
iron	O
oxide	O
nanoparticles	O
.	O
</s>
<s>
SIPPs	B-Algorithm
were	O
also	O
encapsulated	O
with	O
phospholipids	O
to	O
create	O
multifunctional	O
SIPP	O
stealth	O
immunomicelles	O
that	O
specifically	O
targeted	O
human	O
prostate	O
cancer	O
cells	O
.	O
</s>
<s>
The	O
complex	O
specifically	O
targeted	O
human	O
prostate	O
cancer	O
cells	O
in	O
vitro	O
,	O
and	O
these	O
results	O
suggest	O
that	O
SIPPs	B-Algorithm
may	O
have	O
a	O
role	O
in	O
the	O
future	O
as	O
tumor-specific	O
contrast	B-Algorithm
agents	I-Algorithm
.	O
</s>
<s>
Manganese(II )	O
chelates	O
such	O
as	O
Mn-DPDP	O
(	O
Mangafodipir	O
)	O
enhance	O
the	O
T1	B-Algorithm
signal	O
.	O
</s>
<s>
Manganese(II )	O
ions	O
are	O
often	O
used	O
as	O
a	O
contrast	B-Algorithm
agent	I-Algorithm
in	O
animal	O
studies	O
,	O
often	O
called	O
MEMRI	O
(	O
Manganese-Enhanced	O
MRI	O
)	O
.	O
</s>
<s>
A	O
wide	O
variety	O
of	O
oral	O
contrast	B-Algorithm
agents	I-Algorithm
can	O
enhance	O
images	O
of	O
the	O
gastrointestinal	O
tract	O
.	O
</s>
<s>
They	O
include	O
gadolinium	O
and	O
manganese	O
chelates	O
,	O
or	O
iron	O
salts	O
for	O
T1	B-Algorithm
signal	O
enhancement	O
.	O
</s>
<s>
Natural	O
products	O
with	O
high	O
manganese	O
concentration	O
such	O
as	O
blueberry	O
and	O
green	O
tea	O
can	O
also	O
be	O
used	O
for	O
T1	B-Algorithm
increasing	O
contrast	B-Algorithm
enhancement	I-Algorithm
.	O
</s>
<s>
Perflubron	O
,	O
a	O
type	O
of	O
perfluorocarbon	O
,	O
has	O
been	O
used	O
as	O
a	O
gastrointestinal	O
MRI	B-Algorithm
contrast	I-Algorithm
agent	I-Algorithm
for	O
pediatric	O
imaging	O
.	O
</s>
<s>
This	O
contrast	B-Algorithm
agent	I-Algorithm
works	O
by	O
reducing	O
the	O
number	O
of	O
hydrogen	O
ions	O
in	O
a	O
body	O
cavity	O
,	O
thus	O
causing	O
it	O
to	O
appear	O
dark	O
in	O
the	O
images	O
.	O
</s>
<s>
Newer	O
research	O
suggests	O
the	O
possibility	O
of	O
protein	O
based	O
contrast	B-Algorithm
agents	I-Algorithm
,	O
based	O
on	O
the	O
abilities	O
of	O
some	O
amino	O
acids	O
to	O
bind	O
with	O
gadolinium	O
.	O
</s>
