Neuroimaging Assessment of Traumatic Brain Injury - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 259

Hydrogen MRS, also known as proton MRS, may be used to
quantify numerous endogenous neurochemicals such as
N -acetylaspartate (NAA), creatine, PCr, myo-inositol, scyllo-inositol,
glutamine, glutamate, glucose, glutathione, lactate, pyruvate, taurine,
and GABA. Proton MRS is rather more complicated than 31 P-
MRS, since the tissue water signal, which dominates the neuro-
chemical signals by up to seven orders of magnitude, must be
suppressed. Moreover, since skull and subcutaneous fat signals are
extremely strong and can interfere with resonances of greater inter-
est, MRS signals must be localized to discrete brain regions.
Fortunately, sophisticated acquisition sequences are available on
commercial MR instruments to achieve the necessary suppression
rates for high-quality spectroscopy.
Since MRS, like MRI, is noninvasive, longitudinal studies are
feasible. Studies by Schuhmann et al. ( 17 ) have shown that NAA, a
neurochemical produced in the neuronal mitochondria, shows a
postinjury time-course of changes similar to histological evidence of
neuronal pathology. Similarly, choline and myo-inositol, putative
markers of infl ammation, followed similar time-courses to those of
histological markers of infl ammation. Other MRS-visible neuro-
chemicals such as glutamate and glutamine, which are involved in
the glutamatergic neurotransmission system and glutamate excito-
toxicity, and glutathione, an important anti-oxidant species, are
likely to be informative in pathological processes. Accordingly,
proton MRS might be useful in explorations of cellular and molecu-
lar mechanisms of TBI. Proton MRS also has considerable transla-
tional value since it is widely available on commercial clinical scanners
for studies in humans. Several studies have shown that MRS
neurochemical biomarkers such as NAA and choline are strongly
correlated with cognitive recovery following human TBI ( 18, 19 ).
Other nuclei that are of biological signifi cance, such as 13 C
and 15 N, also have MRS signals. These isotopes are low in natural
abundance and their weak endogenous signals are relatively unin-
formative. However, it is possible to introduce metabolites that
are enriched with these isotopes and carry out tracer studies to
determine the metabolic fate of specifi c chemical moieties. Studies
by Bartnik et al. demonstrated upregulated pentose phosphate
metabolism after moderate to severe TBI by following the metabo-
lism of [1,2- 13 C]-labeled glucose as the label is incorporated into
glutamate, glutamine, and lactate ( 20 ). Although the spectroscopic
acquisitions in these particular experiments were carried out in
extracts, they are feasible in the living brain in vivo. Studies using
15 N-labeled species, although to date not implemented in TBI, have
the potential of following amino acid pathways noninvasively.
Magnetic resonance spectroscopy in general has certain
advantages as a tool for metabolic imaging. First, acquisition
sequences for proton MRS are implemented on MRI scanners
using the same hardware confi guration as MRI. Accordingly,