Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates
Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA, United States. Journal of Magnetic Resonance
(Impact Factor: 2.51).
06/2013; 234C:75-81. DOI: 10.1016/j.jmr.2013.06.003
In metabolic MRI with hyperpolarized contrast agents, the signal levels vary over time due to T1 decay, T2 decay following RF excitations, and metabolic conversion. Efficient usage of the nonrenewable hyperpolarized magnetization requires specialized RF pulse schemes. In this work, we introduce two novel variable flip angle schemes for dynamic hyperpolarized MRI in which the flip angle is varied between excitations and between metabolites. These were optimized to distribute the magnetization relatively evenly throughout the acquisition by accounting for T1 decay, prior RF excitations, and metabolic conversion. Simulation results are presented to confirm the flip angle designs and evaluate the variability of signal dynamics across typical ranges of T1 and metabolic conversion. They were implemented using multiband spectral-spatial RF pulses to independently modulate the flip angle at various chemical shift frequencies. With these schemes we observed increased SNR of [1-(13)C]lactate generated from [1-(13)C]pyruvate, particularly at later time points. This will allow for improved characterization of tissue perfusion and metabolic profiles in dynamic hyperpolarized MRI.
Available from: Avigdor Leftin
- "MRSI experiments were conducted using a centric 8×8 phase-encoded matrix spanning a 1.25×1.25 cm2 field of view, beginning 10 s after hyperpolarized bolus injections. Ramped-flip angle  slice-selective Gaussian pulses were used to obtain free induction decays of 512 time points over 100 ms acquisition times (4 kHz spectral bandwidth); as the acquisition time equaled the phase-encode repetition time, total scan times were 6.7 s. MRSI data sets were reconstructed on Matlab and jMRUI-5  by spatial zero-filling to 16×16 and time domain zero filling to 1024 points followed by 15 Hz Lorentzian apodization. "
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ABSTRACT: Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic functional magnetic resonance studies in muscle, the simplicity of our approach makes this technique amenable to a wide range of functional metabolic tracer studies.
PLoS ONE 04/2014; 9(4):e96399. DOI:10.1371/journal.pone.0096399 · 3.23 Impact Factor
Available from: Myriam Marianne Chaumeil
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ABSTRACT: Gain-of-function mutations of the isocitrate dehydrogenase 1 (IDH1) gene are among the most prevalent in low-grade gliomas and secondary glioblastoma. They lead to intracellular accumulation of the oncometabolite 2-hydroxyglutarate, represent an early pathogenic event and are considered a therapeutic target. Here we show, in this proof-of-concept study, that [1-(13)C] α-ketoglutarate can serve as a metabolic imaging agent for non-invasive, real-time, in vivo monitoring of mutant IDH1 activity, and can inform on IDH1 status. Using (13)C magnetic resonance spectroscopy in combination with dissolution dynamic nuclear polarization, the metabolic fate of hyperpolarized [1-(13)C] α-ketoglutarate is studied in isogenic glioblastoma cells that differ only in their IDH1 status. In lysates and tumours that express wild-type IDH1, only hyperpolarized [1-(13)C] α-ketoglutarate can be detected. In contrast, in cells that express mutant IDH1, hyperpolarized [1-(13)C] 2-hydroxyglutarate is also observed, both in cell lysates and in vivo in orthotopic tumours.
Nature Communications 09/2013; 4:2429. DOI:10.1038/ncomms3429 · 11.47 Impact Factor
Available from: John Bringas
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ABSTRACT: To investigate hyperpolarized (13) C metabolic imaging methods in the primate brain that can be translated into future clinical trials for patients with brain cancer.
(13) C coils and pulse sequences designed for use in humans were tested in phantoms. Dynamic (13) C data were obtained from a healthy cynomolgus monkey brain using the optimized (13) C coils and pulse sequences. The metabolite kinetics were estimated from two-dimensional localized (13) C dynamic imaging data from the nonhuman primate brain.
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.
The feasibility of using hyperpolarized [1-(13) C]-pyruvate for assessing in vivo metabolism in a healthy nonhuman primate brain was demonstrated using a hyperpolarized (13) C 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. © 2013 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 01/2014; 71(1):19-25. DOI:10.1002/mrm.25003 · 3.57 Impact Factor
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