Biomedical Engineering Reference
In-Depth Information
required to determine the entire
PCr
Pi
exchange pro-
cess
(50)
. Thus, this simplification can make the in vivo
31
P
MT measurement more robust for rapidly determining the ATP
metabolic flux changes induced by either physiological or patho-
logical perturbations.
↔
ATP
↔
5. Perspective
and Discussion
Despite its low detection sensitivity compared to
1
HMRS,
researchers in the past three decades have revealed the great mer-
its of in vivo heteronuclear MRS for a broad range of biomedical
applications. Two of them (i.e.,
31
Pand
17
O) have been discussed
here in great detail and each method provides a unique tool for
noninvasively studying specific metabolic pathways in the brain
through the measurements of metabolite concentrations and bio-
chemical reaction fluxes. The combination of different in vivo
multinuclear MRS approaches may significantly enhance the MR
capability to perform comprehensive studies concerning brain
physiology, neurochemistry, bioenergetics and their relations to
brain function. This point is addressed by answering the follow-
ing questions:
5.1. Why is in vivo
31
P MT Approach
Attractive and
Promising for
Studying Brain
Bioenergetics?
A large amount of research efforts have been spent since early
1980s for exploring the possibility of determining the ATP
metabolic fluxes using a variety of in vivo
31
PMRSMT
approaches and great progress has been made
(20, 44-46, 49, 50,
103-110, 115, 117)
. Nevertheless, the course for advancing the
in vivo
31
P MRS MT methodology and its clinical application
has been significantly slowed down particularly in brain stud-
ies during the last decade. One of the major causes is proba-
bly in regard to two controversial observations in this research
field. The first one is the inconsistency in the results of the mea-
sured reverse ATP fluxes in the literature (e.g.,
(112-114)
). In
our opinion, this inconsistency is likely caused by the lack of
comprehensive spin-exchange models used in the early research
work. And this controversy can be resolved by using more sophis-
ticated three-spin exchange models for accurately determining
the reverse ATP fluxes for both the CK and ATP
ase
reactions
(45, 46, 50, 115, 116)
.
Another surprising observation has raised question regard-
ing whether the measured forward ATP
ase
reaction flux truly
reflects the oxidative phosphorylation in the mitochondria in a
living organ. The ATP synthesis reaction (i.e.,
R2
in
Figs. 15.1
and 15.13
) catalyzed by the coupled activities of glycolytic
enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
and phosphoglycerate kinase (PGK) have been shown to be a
