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Post
e
sample collection in metabolic composi-
tion is a major concern. Samples are kept cool at
1
Cto4
C and experimental times short to
prevent tissue degradation. Tissue macroscopic
structure is better preserved at low speed, so
the spin rate is kept low
d
around 4 kHz to mini-
mize tissue degradation from mechanical stress
but high enough to move spinning side bands
out of the spectral region of interest. At slower
speeds, in the range of several hundred hertz,
specialized pulse sequence techniques for side
band suppression are required.
131,132
MRS in cancer, such as higher level of choline
containing compounds in brain and breast cancer
and lower citrate concentration in prostate cancer,
has been summarized by Pinker et al. and Gillies
et al.
134,135
An overview of MRI and MRS tech-
niques for oncology can be found in reviews by
Kauppinen et al. and Glunde et al.
133,136
Compared to liquid-state and HR-MAS tech-
niques, MRS is hindered by poorer resolu-
tion and sensitivity. Clinical NMR spectrometers
operate at 64 MHz and 128 MHz (1.5 T and
3.0 T) and higher
field strength systems, 300
MHz (7 T), are used only for research purposes.
137
Similar in trend to liquid-state and HR-MAS
studies, 2D experiments are modi
MAGNETIC RESONANCE
SPECTROSCOPY (MRS)
ed and
employed for better peak resolution and to alle-
viate spectral congestion. To this end, Andronesi
et al. have developed the equivalent of the 2D
1
H-
1
H COSY and TOCSY pulse sequences from
liquid-state NMR for in vivo, localized MRS.
138
Using their 2D LASER-COSY pulse sequence
(localized adiabatic selective refocusing corre-
lated spectroscopy), Andronesi and coworkers
demonstrated the unambiguous detection and
quantitation of 2-hydroxyglutarate (2HG) in vivo
in glioma patients with isocitrate dehydrogenase
1(IDH1) mutation (
Figure 6
).
139
Prior to the
in vivo work, the authors con
In vivo localized magnetic resonance imaging
(MRI) generates grayscale images that give gross
and
ne anatomical details and allow the determi-
nation of tumor size and location. These experi-
ments are
1
H detection experiments, and the
contrast in the grayscale images stems from the
differential longitudinal (T
1
(T1-weighted) and trans-
verse (T
2
(T2-weighted) relaxation rates, diffusion
property, and concentration of water in various
tissue environments. Molecular imaging termed
magnetic resonance spectroscopy (MRS), based
on
1
H,
13
C, and
31
P detection, has emerged as
a noninvasive tool to study cancer metabolism
invivo and canaiddiagnosis, prognosis, and treat-
ment monitoring. MRS can monitor endogenous
metabolites, energy state, pH, Mg
2
þ
activity, and
metabolic
rmed the ex vivo
detection of 2HG on biopsy brain tissue using
HR-MAS 2D
1
H-
1
H TOBSY experiment. Muta-
tions in isocitrate dehydrogenase 1 and 2 result
in abnormal accumulation of 2HG in brain tissues.
2HG peaks in 1D MRS spectra are heavily over-
lapped with peaks from higher abundant gluta-
mate and glutamine, and quantitation using
ux using isotope labeled substrates.
133
1
H detectable metabolites by
The signi
cance of
<
FIGURE 6
2D LASER-COSY spectra in vivo in human subjects at 3 T. (A) An anaplastic astrocytoma patient with
IDH1
R132C
. The 2D LASER-COSY shows at 4.02/1.91 ppm the H
a
-H
b
cross peak of 2HG. Projections along both spectral
dimensions through 2HG cross peak indicate the SNR and spectral quality. The single voxel (3
3cm
3
, red rectangle) was
placed on the FLAIR images to include most of the tumor abnormality. (B) A primary glioblastoma patient (wt-IDH1). The 2D
LASER-COSY does not contain any 2HG cross peak in the H
a
-H
b
region outlined by the green rectangle. Projections through
Glu
3
3.5 cm
3
, red rectangle) was placed on the FLAIR
images to include most of the tumor abnormality. (C) A healthy volunteer (wt-IDH1). 2HG is not found in the H
a
-H
b
region of
2D LASERCOSY outlined by the green rectangle. Projections through Glu
þ
Gln cross peak indicate spectral quality. The single voxel (3.5
3.5
þ
Gln indicate spectral quality. The single voxel
3cm
3
, red rectangle) was placed on the MEMPRAGE images in the white matter of the occipital lobe, in a region
similar to tumor locations from patients in (A) and (B). (From reference #139. Reprinted with permission from AAAS.)
(3
3
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