Biomedical Engineering Reference
In-Depth Information
and its spatial distribution due to physiological perturbation. The
measured CMRO
2
can be quantitatively correlated to other asso-
ciated physiological parameter changes.
Figure 15.9
illustrates
one example showing the quantitative relation between CMRO
2
and CBF: both of them were measured by in vivo
17
O MRS in the
α
-chloralose anesthetized rat under a wide range of physiological
conditions from normothermia to hypothermia
(86)
. It shows a
strong correlation between CBF and CMRO
2
with a linear corre-
lation coefficient of R = 0.97 indicating a tight vascular-metabolic
coupling in the rat brain.
4. How to Apply
In Vivo
31
PMRS
for Studying
Cerebral ATP
Metabolic Fluxes
and Bioenergetics
The ATP metabolism for regulating both ATP production and
utilization plays a fundamental role in cerebral bioenergetics,
brain function and neurodegenerative diseases. Two important
chemical reactions that contribute to the brain ATP metabolism
are the ATP
ase
and CK reactions. They are coupled together and
constitute a three-
31
P-spin chemical exchange system involving
ATP, PCr and Pi (i.e., PCr
Pi). One vital function of this
exchange system is to maintain a stable cellular ATP concentra-
tion ensuring continuous energy supply for sustaining electro-
physiological activity in the brain. Logically, the measures of ATP
metabolic fluxes should be more sensitive to the brain activity and
energy state and their change than that of steady-state ATP and
other HEP concentration. Therefore, they should provide a useful
index reflecting cerebral bioenergetics under various brain states.
It would be, thus, essential to find a noninvasive and reliable tech-
nique being able to assess the cellular exchange rates (or fluxes) of
PCr
↔
ATP
↔
Pi in brain
in situ
. The sole approach for serving this
purpose is the use of in vivo
31
P MRS combined with magnetiza-
tion transfer method
(20,43-47,50,103)
. However, to completely
determine the kinetics and fluxes involved in the PCr
↔
ATP
↔
Pi
exchange requires extensive measurements and information
including three steady-state phosphate metabolite concentrations
(i.e., [ATP], [PCr] and [Pi]) and their intrinsic T
1
values, and
four pseudo first-order chemical reaction rate constants (forward
and reverse rate constants for the CK reaction and the ATP
ase
reaction, respectively)
(50)
. The products of the rate constants
and their related phosphate concentrations can provide four ATP
metabolic fluxes along both forward and reverse reaction direc-
tions in the
PCr
↔
ATP
↔
Pi
exchange system (see
Fig. 15.10
).
Several in vivo
31
P MT methods have been developed such as
conventional two-spin magnetization saturation transfer (CST),
inversion recovery transfer (IT) and two-dimensional chemi-
cal exchange spectroscopy (2D-EXSY)
(44, 45, 49, 104)
.They
↔
ATP
↔
