Dynamic Hyperpolarized Carbon-13 MR Metabolic
Imaging of Nonhuman Primate Brain
Ilwoo Park,1* Peder E. Z. Larson,1James L. Tropp,2Lucas Carvajal,1Galen Reed,1
Robert Bok,1Fraser Robb,2John Bringas,3Adrian Kells,3Philip Pivirotto,3
Krystof Bankiewicz,3Daniel B. Vigneron,1and Sarah J. Nelson1,4
Purpose: To investigate hyperpolarized13C metabolic imaging
methods in the primate brain that can be translated into future
clinical trials for patients with brain cancer.
Methods:13C coils and pulse sequences designed for use in
humans were tested in phantoms. Dynamic
obtained from a healthy cynomolgus monkey brain using the
kinetics were estimated from two-dimensional localized
dynamic imaging data from the nonhuman primate brain.
Results: Pyruvate and lactate signal were observed in both
the brain and the surrounding tissues with the maximum
signal-to-noise ratio of 218 and 29 for pyruvate and lactate,
respectively. Apparent rate constants for the conversion of
pyruvate to lactate and the ratio of lactate to pyruvate showed
a difference between brain and surrounding tissues.
Conclusion: The feasibility of using hyperpolarized [1-13C]-
pyruvate for assessing in vivo metabolism in a healthy nonhu-
man primate brain was demonstrated using a hyperpolarized
13C imaging experimental setup designed for studying patients
with brain tumors. The kinetics of the metabolite conversion
suggests that this approach may be useful in future studies
of human neuropathology. Magn Reson Med 71:19–25, 2014.
13C data were
13C coils and pulse sequences. The metabolite
C2013 Wiley Periodicals, Inc.
Key words: Hyperpolarized carbon-13 magnetic resonance
spectroscopic imaging; dynamic nuclear polarization; pyruvate;
Dynamic nuclear polarization (DNP) in conjunction with
13C MR metabolic imaging offers an exciting method of
assessing in vivo metabolism with a substantial gain in
sensitivity over conventional MR methods (1–5). Recent
studies using hyperpolarized [1-13C]-pyruvate as a sub-
strate have demonstrated utility for examining in vivo
tumor metabolism in rodent brain tumor models (6–8).
These preclinical studies have shown the feasibility of
using this technique for differentiation of tumor from
normal brain tissue, characterization of
patterns between pathologically heterogeneous abnormal
and normal brain tissue, and detection of early response
to treatment in animal models of high-grade gliomas.
The first clinical trial using hyperpolarized13C MR met-
abolic imaging has been successfully performed in patients
with prostate cancer (9). This study showed that there
were no dose limiting toxicities following an injection of
hyperpolarized [1-13C]-pyruvate and demonstrated the fea-
sibility of using this technique for evaluating hyperpolar-
ized pyruvate and its metabolic products in humans.
Although previous studies have shown the potential of
applying DNP technology to brain cancer using rodent
models (6–8), animal experiments with a larger brain
size and an anatomy similar to human brain would be
beneficial in translating this technique to a clinical trial
for patients with brain tumor. The purpose of this study
was to design a strategy for obtaining hyperpolarized13C
metabolic imaging from patients with brain cancer and
to demonstrate its feasibility by acquiring data from a
preclinical primate model.13C coils and pulse sequences
were first tested in phantoms. Dynamic
then obtained from a healthy nonhuman primate brain
using the optimized13C coils and pulse sequences, and
metabolic kinetics were estimated.
13C data were
All experiments were performed using a 3T clinical MRI
system (GE Healthcare, Waukesha, Wisconsin, USA) with
40 mT/m, 150 mT/m/ms gradients, a broadband radiofre-
quency (RF) amplifier, and a multinuclear spectroscopy
hardware package. Two
developed in-house (Fig. 1): a volume transmit-receive
birdcage13C coil with an inner diameter of 28 cm (Fig. 1a)
and a bore-insertable volumetric
13C RF coil configurations were
13C transmit coil with a
1Surbeck Laboratory of Advanced Imaging, Department of Radiology and
Biomedical Imaging, University of California, San Francisco, California,
2Global Applied Science Lab, GE Healthcare, Menlo Park, California, USA.
3Department of Neurosurgery, University of California, San Francisco, Cali-
4Department of Bioengineering and Therapeutic Sciences, University of
California, San Francisco, California, USA.
R01CA154915, Ilwoo Park was supported by a basic research fellowship
from the American Brain Tumor Association.
*Correspondence to: Ilwoo Park, Ph.D., 1700 4thStreet, Room BH-303,
San Francisco, CA 94158. E-mail: email@example.com
Received 20 May 2013; revised 29 August 2013; accepted 26 September
Magnetic Resonance in Medicine 71:19–25 (2014)
C 2013 Wiley Periodicals, Inc.
clamshell hinge for ease of patient loading (10) and a bilat-
eral eight-channel phased array receive coil (11,12) (Fig. 1b
and 1c). The bilateral eight-channel phased array receive
coil consists of two curved panels, with each panel con-
taining a linear arrangement of four coil elements.
In order to assess and compare the performance of two
coils, a human head-shaped phantom containing ethyl-
ene glycol (HOCH2CH2OH, anhydrous, 99.8%, Sigma-
Aldrich, St. Louis, Missouri, USA) was scanned using
the birdcage and clamshell/phased array coil configura-
tions (Fig. 2a). The phantom had the size of a human
head with the following dimensions: right–left ¼ 15 cm,
anterior–posterior ¼ 18 cm, superior–inferior ¼ 22 cm.
For the scan with the clamshell/phased array coils, the
distance between the centers of the two receive coils was
17 cm.13C spectral data were acquired from a slice with
a thickness of 1, 2, 3, and 4 cm using a
dimensional (2D) MR spectroscopic imaging sequence
(echo time/pulse repetition time ¼ 3/3,000 ms, 5 kHz
sweep width, 2,048 spectral points) (6). A 20 ? 20
matrix size with the field of view (FOV) of 20 cm pro-
duced voxel sizes of 1, 2, 3 and 4 cc.
A 9-year-old female cynomolgus monkey (macaca fas-
cicularis, body weight ¼ 4.3 kg) was studied on two
occasions to verify the developed experimental setup for
human brain study. Before each imaging experiment, the
animal was intubated, placed on a heated pad, and
administered inhaled isoflurane anesthesia (1%–3%). A
catheter was placed in the saphenous vein for intrave-
nous administration of the hyperpolarized pyruvate solu-
tion. The animal was transferred to the MR scanner and
placed on a circulating water blanket in the supine posi-
tion. Anesthesia was maintained with a constant deliv-
ery of isoflurane(1%–3%),
monitored using pulse oximetry. Foam pads were used
to stabilize the animal’s head within the RF coil. For the
acquisition using clamshell/phased array coils, the dis-
tance between the centers of the two receive panels was
14 cm. All protocols were approved and followed proce-
dures specified by the University of California, San Fran-
cisco Institutional Animal Care and Use Committee.
Prior to each
anatomical images were obtained in the axial and sagittal
planes using an inversion recovery spoiled gradient echo
(IRSPGR) sequence (echo time/repetition time/inversion
time¼2.5/8.4/400 ms, 25 cm FOV, 256?256 matrix, 3
mm slice thickness, and 5 NEX) from the body coil.
The hyperpolarized [1-13C]-pyruvate was produced
using either a prototype SpinLab (General Electric, Nis-
kayuna, New York, USA) (13) or a HyperSense (Oxford
Instruments, Abingdon, UK) DNP polarizer. For the
SpinLab system, a mixture consisting of 1,000 mL
(?1,280 mg) of C1-labeled pyruvic acid and 15 mM trityl
radical was polarized. For the HyperSense system, a mix-
ture of 200 mL (?260 mg) C1-labeled pyruvic acid and 15
mM trityl radical was used. After ?1.5 hours of micro-
wave irradiation, the hyperpolarized pyruvic acid was rap-
idly dissolved in an aqueous solution with 40 mM Tris,
100 mM NaOH, and 0.3 mM Na2 ethylenediaminetetraace-
tic acid. The hyperpolarized solution was then transferred
13C imaging experiment, T1-weighted
FIG. 1.13C RF coil configurations developed for human brain studies. a: Transmit-receive birdcage volume coil. b: Bilateral eight-
channel13C receive coils. c: Clamshell volumetric13C transmit coil and bilateral eight-channel phased array receive coils. [Color figure
can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
FIG. 2. A human head-shaped phantom containing ethylene glycol (a) was used for the comparison of SNR between the birdcage (c)
and phased array coil (d). A row of spectra in the middle of the phantom (b) was used for SNR comparison.
20Park et al.
to the magnet for13C imaging, and an aliquot of the pyru-
vate solution was used to measure the liquid-state polar-
ization using a custom-built low-field NMR spectrometer.
The final dissolved solution had a concentration of 250
mM (0.38 mmol/kg) pyruvate and pH of 7.5 6 0.3.
acquired from a 20-mm slice through the brain: slice-
localized data with 10?flip angle (echo time/pulse repe-
tition time ¼ 35/3,000 ms, 3 s temporal resolution, 64
total time points), 2D-localized data with a multiband RF
excitation using 20?/4?for lactate/pyruvate flip angle
(echo time/pulse repetition time ¼ 4.6/130 ms, 3 s tem-
poral resolution, 24 total time points) (14) and 2D-
localized data with a variable flip angle multiband RF
excitation (echo time/pulse repetition time ¼ 6.1/130 ms,
3 s temporal resolution, 10 total time points) (15,16). The
2D-localized data had 10 phase encodes in the anterior–
posterior direction and a symmetric echo-planar readout
in the right–left direction, providing 10 ? 10 mm in-
plane resolution. Slice-localized and 2D-localized data
were acquired during or following a 5 s injection of
?6.1 mL [1-13C]-pyruvate (250 mM, 0.38 mmol/kg)
through the saphenous vein. Table 1 shows a summary
of nonhuman primate studies.
phantom were processed with software developed in our
laboratory (17). For the data from the clamshell/phased
array coil configuration, the individual spectra were
added as the square root of the sum of the square with
an equal weight for all channels. The signal-to-noise
ratios (SNR) were calculated as the magnitude peak
height over the standard deviation (SD) of the first 200
points of the spectra in a region that contained no signal.
The spatial variation of signal across the phantom was
13C dynamic spectroscopic data were
13C 2D MR spectroscopic imaging data from the
compared between the birdcage and clamshell/phased
array coils for different voxel sizes. The slice-localized
13C dynamic data were processed with MATLAB 7.0
(Mathworks Inc., Natick, Massachusetts, USA). Individ-
ual FIDs were apodized with a 10-Hz Lorentzian filter in
the time domain and Fourier-transformed to produce13C
spectra at each time point. The 2D-localized13C dynamic
data were processed using MATLAB scripts developed
in our laboratory (17). The k-space FIDs were apodized
by a 10-Hz Gaussian filter in the time domain and zero-
filled to 256 points. The data were then Fourier-
transformed to produce a 3D spatial and temporal array.
An additional linear phase correction was applied in the
symmetric echo-planar dimension to correct for the offset
of individual k-space points (14). For the 2D-localized
dynamic data that were acquired using variable flip
angle excitation, the lactate and pyruvate signals were
corrected for the differential flip angle, and apparent rate
constants for the conversion of pyruvate to lactate (KPL)
were estimated using a two-site exchange model (18) for
voxels where the maximum SNR of pyruvate were >40.
The spatially dependent SNR characteristics of the two
coils used for this study is shown in Figure 2. The SNRs
from a row of spectra in the middle of the phantom were
plotted against the relative location in right–left direction
for each coil (Fig. 2c and 2d). The birdcage coil pro-
duced a relatively uniform signal across the phantom
and its SNR increased linearly with an increase in voxel
volume (Fig. 2c). The mean SNR in the center 4 voxels
from the birdcage coil was 10.6, 20.8, 30.4, and 39.4 for
1, 2, 3, and 4 cc voxels, respectively (Table 2). The signal
Summary of Nonhuman Primate Studies
20?/4?flip angle for
Pyruvate Injection (mL)
20?/4?flip angle for
variable flip angle
The second examination was performed 7 days after the first examination using the same animal.
aThe liquid state polarization was corrected to the level at the time of pyruvate dissolution assuming a pyruvate T1of 60s at 3T.
Comparison of SNR Between13C Birdcage and Clamshell/Phased Array Coils from Ethylene Glycol Head Phantom
Voxel size (cc)Birdcagea
10.6 6 0.9
20.8 6 1.6
30.4 6 1.5
39.4 6 2.8
13.1 6 2.8
25.7 6 0.8
39.2 6 3.6
50.8 6 5.2
Maximum SNR in Clamshell/Phased Arrayb
aSNR was calculated from 4 voxels in the middle. All values are reported as the mean 6 SD.
bMaximum SNR was taken from the row of spectral grid that was used to calculate the mean SNR in 4 voxels in the middle.
Hyperpolarized13C Metabolic MRI of Nonhuman Primate Brain 21
from the clamshell/phased array coils appeared to be
highest in the voxels closest to the paddle array and
dropped as the distance from the coil increased (Fig. 2d).
The mean SNR in the center 4 voxels from the clam-
shell/phased array coils was 13.1, 25.7, 39.2, and 50.8
for 1, 2, 3, and 4 cc voxel, respectively (Table 2), which
was an average of 26% higher than the birdcage coil.
The maximum SNR near the coils was 4 to 5 times
higher than the mean SNR in the middle for the clam-
shell/phased array coil setup.
The use of hyperpolarized [1-13C]-pyruvate provided
sufficient signal to detect the transfer of13C label to lac-
tate in nonhuman primate brain. Figure 3 shows slab-
localized13C dynamic data from a 20 mm slice of brain.
Figure 3a shows a sagittal image illustrating the slice
coverage of the hyperpolarized13C dynamic data acquisi-
tion. Figure 3d shows representative13C dynamic spectra
from the13C clamshell/phased array coils. Each horizon-
tal line corresponds to a summed magnitude spectrum
acquired at a time resolution of 3 s. The SNR of pyruvate
and lactate were plotted as a function of time for bird-
cage (Fig. 3b) and clamshell/phased array (Fig. 3c) coils.
The pyruvate signal (173 ppm) reached a maximum at
?12 s after the start of the pyruvate injection, while the
lactate signal maximum (185 ppm) was at ?24 seconds.
The lactate signal maintained a relatively constant level
for 12–15 s at the maximum value. The pyruvate signal
decreased rapidly from the maximum peak, and the lac-
tate signal decreased at a slightly slower rate than the
pyruvate. [1-13C]-pyruvate–hydrate was also observed
between pyruvate and lactate resonances, but had rela-
tively low signal amplitude (Fig. 3d).
from the brain of the nonhuman primate allowed for the
temporally and spatially resolved imaging of pyruvate
and lactate. Figure 4a and 4b shows a pyruvate signal
map over time from the 2D-localized data acquired with
the 20?/4?lactate/pyruvate flip angle scheme using the
birdcage and clamshell/phased array coils, respectively.
The pyruvate signal appeared throughout the brain and
quickly reached its maximum at 9 s from the end of
pyruvate injection. The maximum pyruvate SNR was 67
13C dynamic spectroscopic imaging
and 218 for the birdcage and clamshell/phased array
coil, respectively. Figure 4c–4e illustrates the data from
the 2D-localized data acquired with the variable flip
angle scheme using the clamshell/phased array coils.
The maximum SNR of pyruvate and lactate were 177
and 29, respectively. The pyruvate signal in the brain
reached its maximum at 9 s from the end of injection,
and the lactate signal at 30 s (Fig. 4c). When corrected
for the variable flip angle, the maximum lactate appeared
at 18 s (Fig. 5). A representative axial image and the cor-
responding magnitude spectra acquired at 30 s with the
clamshell/phased array coils are illustrated in Figure 4d.
Both pyruvate (blue arrow) and lactate peak (red arrow)
were detected in brain as well as surrounding tissue.
Figure 5 shows the overlay image of apparent rate con-
stants for the conversion of pyruvate to lactate and exam-
ples of time courses of pyruvate and lactate with the
corresponding curve fits from the data acquired with the
variable flip angle scheme using the clamshell/phased
array coils (exam 2c in Table 1). The pyruvate and lac-
tate signals were corrected for the variable flip angles.
KPLwas 0.0026 6 0.0004 s?1(mean 6 SD, n ¼ 13) for
the voxels within the brain (Fig. 5b) and 0.0042 6
0.001 s?1(mean 6 SD, n ¼ 18) for the voxels surround-
ing the brain (Fig. 5c), which included brain tissue, mus-
cle, and vasculature. The mean standard error estimated
from the covariance matrix of the model fitting was
0.0007 s?1for the voxels within the brain and 0.001 s?1
for the voxels surrounding the brain.
In this study, we established a hyperpolarized13C meta-
bolic imaging method designed for application to human
brain. The proposed pulse sequences and13C coils were
tested using a phantom with the size of a human head
and a nonhuman primate brain. Nonhuman primate was
a good fit for this study because its brain is large and has
a structure similar to human brain. To our knowledge,
this study demonstrated for the first time the use of
hyperpolarized13C imaging to study in vivo brain metab-
olism in a primate brain. Excellent pyruvate and lactate
FIG. 3. Slab-localized dynamic
courses of pyruvate and lactate signal were plotted over time for the data acquired from the birdcage (b) and clamshell/phased array
coils (c). The pyruvate signal was scaled by 0.1 for ease of viewing. The stack plot of13C magnitude spectra from the clamshell/phased
array coils shows an uptake of pyruvate and its metabolic products following the injection of hyperpolarized pyruvate (d).
13C data were acquired from a 20-mm slab through the brain of nonhuman primates (a). The time
22 Park et al.
FIG. 5. a: Map of apparent rate constants for the conversion of pyruvate to lactate from a nonhuman primate brain. Time courses of
pyruvate and lactate, which were corrected for the variable flip angle scheme and the corresponding curve fits, are shown for a repre-
sentative voxel within (b) and surrounding (c) the brain. The pyruvate signal was scaled by 0.2 for ease of viewing.
FIG. 4. 2D-localized dynamic13C spectro-
scopic data: pyruvate maps acquired with
scheme using the birdcage coil (a, exami-
nation 1b in Table 1) or the clamshell/
phased array coils (b, examination 2b in
acquired with the clamshell/phased array
coils and variable flip angle scheme (c,
examination 2c in Table 1), the corre-
sponding13C spectra (d), and the map of
the ratio of lactate over pyruvate (e) at 30s
from the end of pyruvate injection. High
pyruvate and lactate signal were observed
at the last time point in panel c as a result
of the 90?flip angle from the variable flip
angle scheme. The red arrow in panel d
represents the lactate peak; the blue arrow
represents the pyruvate peak. The lactate
and pyruvate signal maps were normalized
to the corresponding maximum signal.
Hyperpolarized13C Metabolic MRI of Nonhuman Primate Brain23
signal were observed in the primate brain as well as its
The SpinLab is a new polarizer design with specifica-
tions that are focused on clinical use with a large volume
of substrate polarization and dissolution process. Our
study was the first to use the SpinLab system for animals
larger than rodents. One of the reasons for using the two
polarizers in this study was to establish the feasibility of
using the SpinLab by comparing with the more well-
established HyperSense system. Both systems were able
to generate hyperpolarized pyruvate solutions. One of
the polarization measurements had a relatively low level
of polarization (Table 1). We believe that air bubbles in
the syringe that contained the aliquot of pyruvate solu-
tion for polarization measurement caused the low polar-
solution in the syringe was applied in the subsequent
polarization measurements. On average, the SpinLab sys-
tem produced a 50% higher polarization than the Hyper-
Sense system (Table 1). This increase was due to the
lower sample vial temperature in the SpinLab system
(?1 K) compared with the HyperSense system (1.2 K)
(19). The ability to produce the higher level of polariza-
tion and larger volumes for rapid, successive injections
makes the SpinLab system a promising tool to probe13C
metabolism in future preclinical and clinical studies.
The birdcage and clamshell/phased array coils dis-
played a distribution of signal across the phantom with
the size of human head. The birdcage coil rendered rela-
tively uniform signal across the phantom. In comparison
to the birdcage coil, the clamshell/phased array setup
produced on average 26% higher signal in the middle of
the phantom (Table 2). The clamshell/phased array coils
produced on average 179% higher signal in the region
close to the receive coil surface compared with the
region in the middle. Two linear panels in the phased
array coils contain the linear arrangement of four surface
coils (Fig. 1b), which contributed to a decrease in signal
toward the center of the phantom. One should be careful
to avoid the misinterpretation of metabolite signal inten-
sity because it depends on the relative location of the
voxel to the coils. One way to overcome this issue is to
use the apparent rate constant for pyruvate to lactate
conversion (Fig. 5) or the ratio of lactate to pyruvate (Fig.
4e) for quantification.
Previously, we successfully acquired 2D dynamic data
with an echo planar readout gradient (14), and estab-
lished the feasibility of this method for acquiring human
data from prostate cancer patients (9). However, The
majority of previous experiments using 2D dynamic
imaging were performed with a fixed flip angle method.
The use of a variable flip angle has been proposed as a
method to preserve the pyruvate and lactate magnetiza-
tion for a longer period and hence allow the more sensi-
tive detection at a time when more of the pyruvate has
been converted to lactate (16). We started with the pro-
ven method that uses a fixed flip angle in the first scan
session and in the second scan session, we then acquired
data with both the fixed and variable flip angle scheme
in order to compare the two methods. The voxel resolu-
tion (2 cm3) for 2D dynamic acquisition was chosen to
replicate the voxel resolution that will be used for the
upcoming clinical trial with brain tumor patients. The
choice of temporal resolution was based on the balance
between the amount of signal observed per image and
the total number of time points required for the kinetic
modeling. From our experience in previous experiments
with rodent models, we selected 3 s temporal resolution
as the time resolution for our current study (14,18).
The excellent SNR and spectral quality from the 2D-
of the spatial distribution of metabolites and their evolu-
tion over time. A high level of pyruvate and lactate sig-
nalwas observed throughout
surrounding tissue. The pyruvate signal peaked shortly
after the injection and decreased rapidly from its maxi-
mum. When corrected for the variable flip angle scheme,
the maximum lactate in the brain appeared ?9 s after the
maximum pyruvate peak (Fig. 5b), which was consistent
with the findings from a previous study using healthy
and glioma-bearing rat brains (6).
Differences in estimated metabolic parameters were
observed in different regions around the primate brain.
Voxels within cerebral hemispheres produced large
pyruvate signal, while voxels surrounding the brain
appeared to produce relatively low pyruvate signal but
exhibited the highest lactate signal (Fig. 4c). The esti-
mated KPL was higher in voxels surrounding the brain
compared with voxels within the brain (Fig. 5a). The rel-
atively low SD of KPLacross normal brain voxels suggests
the robustness of this method to provide a useful base-
line for characterizing metabolite kinetics in patients
with brain tumors. Similarly, the ratio of lactate to pyru-
vate was higher in tissue outside the brain (mean 6 SD:
0.30 6 0.08) compared with the cerebral hemispheres
(mean 6 SD: 0.25 6 0.03) (Fig. 4e). The lactate-to-
pyruvate ratio within the primate brain was similar to
the one estimated from normal rat brains (6,8). Although
the quantification of these metabolic parameters was
affected by the relatively coarse spatial resolution caus-
ing partial volume effects, they were less sensitive to
imaging factors such as polarization, injection time, and
volume. The estimated KPL and the ratio of lactate to
pyruvate may provide a robust and useful way to quan-
tify in vivo metabolism in both normal and pathologic
human brain tissue.
A recent hyperpolarized
investigated the effect of anesthesia level on the cerebral
substrate and metabolite signal in rat brain and demon-
strated the dependence of cerebral substrate signal levels
on isoflurance dose (21). The results from this study may
not be directly comparable to a clinical study with brain
tumor patients, who will undergo hyperpolarized
imaging experiment without anesthesia. The expected
level of substrate and metabolite in a clinical study and
its comparison with the current study are beyond the
scope of this paper.
Future studies will apply the pulse sequences and13C
coils proposed in this study to assess the safety and fea-
sibility of acquiring hyperpolarized13C metabolic imag-
ing data from patients with brain tumors. In particular,
they will seek to confirm the findings from previous pre-
clinical studies using a glioma model (7,20), which dem-
onstrated a significant reduction in
13C imaging enabled the assessment
13C MR imaging study has
24Park et al.
within a few days after treatment, and to investigate the Download full-text
feasibility of this technique as a new imaging tool for
detecting early response to therapy in patients with brain
We established a hyperpolarized
experimental design that is appropriate for studying
patients with brain tumors and demonstrates the feasibil-
ity of using hyperpolarized [1-13C]-pyruvate for assessing
in vivo metabolism in a healthy nonhuman primate
brain. Signals from pyruvate and lactate were observed
in both the brain and the surrounding tissues. The high
SNR of pyruvate and lactate within normal brain indi-
cates that pyruvate is able to cross the blood–brain bar-
rier and provide signals that can be measured using the
pulse sequences and coils that we have developed. The
kinetics of the metabolite conversion showed that this
approach might be useful in characterizing the brain and
its surrounding tissues.
13C metabolic imaging
We gratefully acknowledge the assistance of Bert Jime-
nez, R.N., and Mary Mcpolin, R.T., for assisting with
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