Biomedical Engineering Reference
In-Depth Information
functional brain imaging. Recently, due to better sensitivity at
high magnetic fields,
31
P MRS has been able to measure forward
and backward fluxes of creatine kinase
(81)
. Although the tem-
poral resolution of this approach is still low (seconds to minutes),
there is great potential of its use because comparable techniques
do not exist yet.
Similar to
31
PMRS,
17
O MRS was also demonstrated nearly
two decades ago
(82)
and due to recent advancements, the
method has been revitalized
(83)
.The
17
O MRS method for oxy-
gen consumption follows almost the same approach as
15
OPET
(i.e., inhale labeled-oxygen and detect labeled-water). However,
a key difference between the two methods is that
17
O MRS can
distinguish between labeled-water (very strong MRS signal) and
labeled-oxygen (exceptionally weak MRS signal), whereas PET
cannot. This allows for removal of a few assumptions for modeling
oxygen consumption with
17
OMRS.The
17
O MRS method can
also measure blood flow and follows the same principles as
15
O
PET (i.e., inject labeled-water and detect loss of labeled-water).
Although
19
F is intrinsically almost as sensitive as
1
Hand
it is naturally 100% abundant
(78)
, there are no biomolecules
in vivo (of relevance) containing fluorine. Therefore FDG, as in
PET, has been applied with
19
F MRS for glucose consumption
measurement
(84)
, but the MRS tracer is not radioactive. Fur-
thermore,
19
F MRS can distinguish between FDG-6-phosphate
created by metabolism of FDG from FDG itself, whereas
18
F
PET cannot. Dynamic separation between the amount of FDG-
6-phosphate and FDG helps quantify the glucose consumption
rate. For
19
F MRS detection of these signals with modest signal-
to-noise ratio, either very high FDG doses (
10mM)havebeen
used with acceptable acquisition times or very long acquisition
times (hours) have been used with low FDG doses (
>
1mM).
More recently, due to superior sensitivity at high magnetic fields,
19
F MRS with reasonable spatial (mm range) and temporal res-
olution (
<
<
30 min) has been demonstrated using a low FDG
dose
(85)
.
Glucose consumption measured by the FDG method (MRS
or PET) has a non-oxidative and oxidative component, where
the latter can be measured by
13
C MRS. Although
13
C detec-
tion sensitivity is quite low (see above), using
13
C-labeled exoge-
nous biomolecules provides a viable alternative because of com-
partment/substrate specific information.
13
C MRS is a very pow-
erful tool to study metabolism when it is used in combina-
tion with a
13
C-labeled substrate, such as [1-
13
C]glucose
(86)
.
Infusion of [1-
13
C]glucose (into the blood stream) results in
13
C turnover into glucose, glutamate, glutamine, GABA, lactate,
aspartate, etc, in brain tissue
(25, 42)
.Since
13
C turnover into
these pools is time dependent, coupled differential equations can
be used to estimate a range of fluxes (including neuronal/glial