Biomedical Engineering Reference
In-Depth Information
to noninvasively detect and quantify the cerebral metabolic rate
of oxygen utilization (CMRO
2
) and ATP formation (CMR
ATP
),
therefore, become extremely important for studying and under-
standing the relation between ATP metabolism and cerebral
bioenergetics and its impact on brain function.
1.2. In Vivo
Heteronuclear MRS
Approaches for
Studying Brain
Bioenergetics and
Function
Although there are a number of techniques capable of studying
brain metabolism, in vivo heteronuclear magnetic resonance spec-
troscopy (MRS) allows for noninvasively determining the physi-
ological parameters and their changes that can be linked to brain
metabolism, chemical kinetics and cerebral bioenergetics. The
most commonly used in vivo heteronuclear MRS approaches for
studying brain bioenergetics are in vivo
31
P,
13
Cand
17
OMRS.
Here,wewillfocuson
31
Pand
17
O MRS in vivo.
In vivo
31
P MRS allows noninvasive assessment of numer-
ous fundamental biochemical, physiological and metabolic events
occurring inside a living brain (e.g.,
(17-23)
). The primary infor-
mation provided by in vivo
31
P MRS includes: intracellular pH,
intracellular free magnesium concentration ([Mg
2
+
]) and high-
energy phosphate (HEP) metabolites such as ATP, ADP and PCr.
All these phosphate metabolites (except ADP) and Pi can be
directly observed in an in vivo
31
P MR spectrum as demonstrated
in
Fig. 15.2A
which was acquired from the human occipital-
lobe at high field (7 tesla)
(24)
. The pH value can be calculated
from the chemical shift difference (
δ
i
) between the Pi and PCr
resonance peaks according to the following equation:
(25)
log
δ
i
−
3. 29
5. 68
pH
=
6. 77
+
(15.1)
−
δ
i
and [ADP] can be calculated by the following equation:
]=
[
]
[
]−[
]
ATP
(
Cr
PCr
)
[
ADP
(15.2)
K
eq
[
PCr
][
H
+
]
where
K
eq
is the equilibrium constant of the creatine kinase reac-
tion and [Cr] is the total creatine concentration given by the sum-
mation of PCr and non-phosphorylated Cr.
Besides the aforementioned phosphate compounds and
physiological parameters, other detectable phosphate compounds
in the human brain
31
P MRS include: uridine diphospho
(UDP) sugar (an important precursor for glycogen metabolism),
diphospho nicotinamide adenine dinucleotides (NAD) involv-
ing oxidative respiratory chains, and four resolved phosphate
compounds
of
glycerophosphoethanolamine
(GPE),
glyc-
erophosphocholine
(GPC),
phosphoethanolamine
(PE)
and
phosphocholine
(PC),
which
are
actively
involved
in
the
membrane
phospholipid
metabolism
through
phospholipid
