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
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