Maninder Singh1, Sonal Josan2, and Dirk Mayer1
1Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, United States, 2Siemens Healthcare, Erlangen, Germany
Synopsis
Metabolic
imaging of biologically-relevant hyperpolarized agents allows measurement of
metabolic processes in real time in-vivo. We demonstrate dynamic metabolic
imaging of a single bolus of co-polarized [2-13C]pyruvate and [1,4-13C2]fumarate
in control as well as in rats with liver necrosis. Chemical shift imaging (CSI)
of such a mixture is challenging due to the large spectral dispersion of resulting
resonances, which could lead to severe chemical shift displacement artifacts if
acquired by conventional slice-selective excitation pulses. Here we obtain CSI
information by a volumetric method using alternate 3D spectrally-selective
excitation of sub-bands containing fewer resonances.
Introduction
Metabolic
imaging of hyperpolarized 13C-labeled pyruvate (Pyr) and fumarate (Fum)
has shown great potential in characterizing multiple diseases and assessing response
to treatment, especially in cancer.1 Performing
these measurements with a single injection of co-polarized substrates would be
advantageous particularly for the clinical translation of this technology. Recently,
a study reported on combined metabolic imaging of [1-13C]Pyr and
[1,4-13C2]Fum in a rat model of necrosis.2 However, the small chemical shift (CS)
dispersion of both substrates and their metabolic products (~25 ppm) does not allow
using signal-to-noise (SNR)-efficient differential flip angles for substrate
and products3 at clinical field strengths, potentially preventing the
measurement of their saturation kinetics that requires effective 90° excitation
of the products.4 Therefore, the goal of this study was investigating
the feasibility of simultaneous metabolic imaging of co-polarized [2-13C]Pyr
and [1,4-13C2]Fum with different excitation flip angles on
a clinical MR scanner taking advantage of the much larger CS dispersion of [2-13C]Pyr
and its products [2-13C]lactate (Lac) and [2-13C]alanine
(Ala) (>160 ppm). Methods
Our
method is based on 3D spiral chemical shift imaging (spCSI) developed for
metabolic imaging of [2-13C]Pyr.5 To avoid CS
displacement artifacts due to the large CS dispersion, the sequence applied frequency-selective
RF pulses to alternatingly excite two spectral sub-bands each one followed by a
fast 3D-spCSI readout. Although
implemented on a clinical MR scanner, that study used a high-performance
gradient insert to achieve a high spectral width (SW) of ~500 Hz with only 2
spatial interleaves to sufficiently separate the multiple resonances. However,
on our GE 3T 750w MR scanner with maximum gradient strength of 33 mT/m and slew
rate of 120 mT/m/ms, achieving this SW would require about 20 spatial interleaves
for the same spatial parameters, hence, leading to unacceptable scan times of
24 s per band. Therefore, we applied number of signal averages (NSA) analysis used
in least-squares estimation imaging approaches6,7
to investigate if smaller SW would be sufficient. For dynamic imaging, we
applied the two RF pulses shown in Fig. 1. The 14 ms pulse for band-1 only excites Fum (2.5°)
and both malate (Mal) resonances (10°). The 2.8 ms pulse for band-2 only
excites resonances from Lac, Ala, and Pyr hydrate (Pyh), all with a 10°
excitation flip angle. Pyh is measured instead of Pyr itself as
it is in exchange with Pyr and not metabolically active. For the design of the
RF pulses it is in important to sufficiently suppress excitation of Pyr in both
bands and of Fum during excitation of band-2. The performance of the pulses was tested on a
sample of co-polarized Pyr and Fum using a simple pulse-and-acquire MRS
sequence that alternatingly used the two pulses (TR = 3 s) for 90 s. This
acquisition was followed by the same sequence but using a 32-µs hard pulse
(5.625°) for 4min. Co-polarization of the two substrates to about 35% was
performed similarly as described in Ref. 2 using a GE SPINlab polarizer
operating at 5T and 0.9K. In vivo
experiments using dynamic 3D-spCSI were done in control as well as in rats with
liver necrosis induced by CCl4 administration. A single-loop 13C
surface coil placed on top of the liver was used for both signal excitation and
reception.Results and Discussion
The
NSA plots shown in Fig. 2 indicate an echo shift of 3.87 ms (corresponding to a
SW of 258Hz) is sufficient to separate metabolites excited in the two
alternating bands. The feasibility of our strategy is demonstrated by the
time-averaged CSI data from a rat with CCl4-induced necrosis shown
in Fig. 3. The spectra from an ROI in the liver show how well the peaks are
separated in the spectra from different bands. In band-1, the SW is sufficient
to detect both Fum and Mal peaks without aliasing. However, for band 2, relative
to Lac, the Ala peaks were aliased -2 times and Pyh 3 times. This required
separate reconstructions for the aliased signals to properly demodulate the
phase.8 The corresponding metabolic maps are shown in Fig. 4. From
the MRS measurement of the Pyr/Fum solution we calculated the residual
excitation flip angle of the substrate resonances as: for Pyr 0.004° in
band-1 and 0.015° in band-2, and for Fum 0.006° in band-2. The spectra from a
liver ROI in a healthy control animal after injections of co-polarized Pyr/Fum
and Pyr only also indicate sufficient suppression of Pyr (Fig. 5a). Metabolite
time courses from liver ROIs demonstrate feasibility of dynamic imaging with a
time resolution of 4.5 s per band (Fig. 5b).Acknowledgements
This work was supported by NIH
grants R01 DK106395, R21 CA213020, R21 CA202694, and R21 NS096575.References
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