Biomedical Engineering Reference
In-Depth Information
metabolism (i.e. reaction rate constants and fluxes) should logi-
cally be more sensitive and meaningful for quantifying the cere-
bral bioenergetics and its change under varied brain activity states
as compared to the measurement of steady-state ATP concentra-
tions. In vivo
31
P MRS, in combination with the magnetization
transfer (MT) approach
(18, 43-48)
, is capable of noninvasively
determining the chemical reaction fluxes related to the ATP
metabolism and enzyme activity; and thus becomes an impor-
tant tool for studying the brain ATP metabolisms and cerebral
bioenergetics. One example is to apply this approach for measur-
ing the metabolic flux of oxidative phosphorylation in the brain
(20,49,50)
. This useful in vivo approach and its new development
will be described here.
Another alternative in vivo heteronuclear MRS approach
which can directly and noninvasively assess the fluxes of oxida-
tive metabolism occurring in the mitochondria (i.e.,
R1
in
Fig. 15.1
)istheuseofinvivo
17
O MRS approach for imaging
CMRO
2
(e.g.,
(51-54)
and a recent review article
(55)
and the
references cited therein). The basic idea underlying this approach
is to apply in vivo
17
O MRS for detecting the dynamic change of
the
17
O-labeled metabolic water (H
2
17
O) produced through the
metabolism of inhaled
17
O
2
gas, and ultimately for determining
and imaging CMRO
2
. Recent progress, especially at ultrahigh
fields, has advanced the in vivo
17
O MRS methodology for
imaging CMRO
2
and great promise has been demonstrated in
the animal applications at high fields. This topic is also discussed
here in some detail.
Although the metabolic fluxes measured by in vivo
31
PMRS
andinvivo
17
O MRS reflect different metabolic reactions and
pathways, these two MRS approaches are quite complementary.
They are vital for investigating the coupling between the oxygen
utilization and oxidative phosphorylation in the brain mitochon-
dria under normal and pathological conditions.
2. Benefit of In
Vivo
31
Pand
17
O
MRS at Ultrahigh
Magnetic Field
In practice, in vivo heteronuclear MRS faces many technical
challenges due to its unfavorable sensitivity. For instance, the
phosphate metabolites detected by in vivo
31
PMRSandthe
metabolic H
2
17
O detected by in vivo
17
O MRS are in a range
of few millimolar concentrations, which are approximately 5000
times lower than the tissue water concentration, resulting in a
much lower detection sensitivity. Thus, a high number of signal
averaging is required to achieve reasonable spectral quality. This
2.1. Challenges of In
Vivo Heteronuclear
MRS
