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Register a new userA Metabolite Specific 3D Stack-of-Spiral bSSFP Sequence for Improved Lactate Imaging in Hyperpolarized [1-$^{13}$C]Pyruvate Studies on a 3T Clinical Scanner
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Purpose: The balanced steady-state free precession sequence has been previously explored to improve the efficient use of non-recoverable hyperpolarized $^{13}$C magnetization, but suffers from poor spectral selectivity and long acquisition time. The purpose of this study was to develop a novel metabolite-specific 3D bSSFP (MS-3DSSFP) sequence with stack-of-spiral readouts for improved lactate imaging in hyperpolarized [1-$^{13}$C]pyruvate studies on a clinical 3T scanner. Methods: Simulations were performed to evaluate the spectral response of the MS-3DSSFP sequence. Thermal $^{13}$C phantom experiments were performed to validate the MS-3DSSFP sequence. In vivo hyperpolarized [1-$^{13}$C]pyruvate studies were performed to compare the MS-3DSSFP sequence with metabolite specific gradient echo (MS-GRE) sequences for lactate imaging. Results: Simulations, phantom and in vivo studies demonstrate that the MS-3DSSFP sequence achieved spectrally selective excitation on lactate while minimally perturbing other metabolites. Compared with MS-GRE sequences, the MS-3DSSFP sequence showed approximately a 2.5-fold SNR improvement for lactate imaging in rat kidneys, prostate tumors in a mouse model and human kidneys. Conclusions: Improved lactate imaging using the MS-3DSSFP sequence in hyperpolarized [1-$^{13}$C]pyruvate studies was demonstrated in animals and humans. The MS-3DSSFP sequence could be applied for other clinical applications such as in the brain or adapted for imaging other metabolites such as pyruvate and bicarbonate.
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Purpose: Hyperpolarized imaging experiments have conflicting requirements of high spatial, temporal, and spectral resolution. Spectral-Spatial RF excitation has been shown to form an attractive magnetization-efficient method for hyperpolarized imaging, but the optimum readout strategy is not yet known. Methods: In this work we propose a novel 3D hybrid-shot spiral sequence which features two constant density regions that permit the retrospective reconstruction of either high spatial or high temporal resolution images post hoc, (adaptive spatiotemporal imaging) allowing greater flexibility in acquisition and reconstruction. Results: We have implemented this sequence, both via simulation and on a pre-clinical scanner, to demonstrate its feasibility, in both a 1H phantom and with hyperpolarized 13C pyruvate in vivo. Conclusion: This sequence forms an attractive method for acquiring hyperpolarized imaging datasets, providing adaptive spatiotemporal imaging to ameliorate the conflict of spatial and temporal resolution, with significant potential for clinical translation.
Purpose: Acquisition timing and B$_1$ calibration are two key factors that affect the quality and accuracy of hyperpolarized $^{13}$C MRI. The goal of this project was to develop a new approach using regional bolus tracking to trigger Bloch-Siegert B$_1$ mapping and real-time B$_1$ calibration based on regional B$_1$ measurements, followed by dynamic imaging of hyperpolarized $^{13}C$ metabolites in vivo. Methods: The proposed approach was implemented on a system which allows real-time data processing and real-time control on the sequence. Real-time center frequency calibration upon the bolus arrival was also added. The feasibility of applying the proposed framework for in vivo hyperpolarized $^{13}$C imaging was tested on healthy rats, tumor-bearing mice and a healthy volunteer on a clinical 3T scanner following hyperpolarized [1-$^{13}$C]pyruvate injection. Multichannel receive coils were used in the human study. Results: Automatic acquisition timing based on either regional bolus peak or bolus arrival was achieved with the proposed framework. Reduced blurring artifacts in real-time reconstructed images were observed with real-time center frequency calibration. Real-time computed B$_1$ scaling factors agreed with real-time acquired B$_1$ maps. Flip angle correction using B$_1$ maps results in a more consistent quantification of metabolic activity (i.e, pyruvate-to-lactate conversion, k$_{PL}$). Experiment recordings are provided to demonstrate the real-time actions during the experiment. Conclusion: The proposed method was successfully demonstrated on animals and a human volunteer, and is anticipated to improve the efficient use of the hyperpolarized signal as well as the accuracy and robustness of hyperpolarized $^{13}$C imaging.
Purpose: To develop an approach for improving the resolution and sensitivity of hyperpolarized 13C MRSI based on a priori anatomical information derived from featured, water-based 1H images. Methods: A reconstruction algorithm exploiting 1H MRI for the redefinition of the 13C MRSI anatomies was developed, based on a modification of the Spectroscopy with Linear Algebraic Modeling (SLAM) principle. To enhance 13C spatial resolution and reduce spillover effects without compromising SNR, this model was extended by endowing it with a search allowing smooth variations in the 13C MR intensity within the targeted regions of interest. Results: Experiments were performed in vitro on enzymatic solutions and in vivo on rodents, based on the administration of 13C-enriched hyperpolarized pyruvate and urea. The spectral images reconstructed for these substrates and from metabolic products based on predefined 1H anatomical compartments using the new algorithm, compared favorably with those arising from conventional Fourier-based analyses of the same data. The new approach also delivered reliable kinetic 13C results, for the kind of processes and timescales usually targeted by hyperpolarized MRSI. Conclusions: A simple yet flexible strategy is introduced to boost the sensitivity and resolution provided by hyperpolarized 13C MRSI, based on readily available 1H MR information.
It was demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with ultraviolet (UV) light, enabling radical-free dissolution DNP. Although pyruvate is endogenous, an excess of additional pyruvate may perturb metabolic processes, making it potentially unsuitable as a polarizing agent when studying fatty acids or carbohydrate metabolism. Therefore, the aim of the study was to characterize solutions containing endogenously-occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (AKV) and alpha-ketobutyrate (AKB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing AKV and AKB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with ESR and compared to pyruvate. The addition of 13C labeled substrates to the sample matrix altered the radical yield of the precursors. Using AKB increased the 13C-labeled glucose liquid state polarization to 16.3 +/- 1.3% compared with 13.3 +/- 1.5% obtained with pyruvate, and 8.9 +/- 2.1% with AKV. For [1-13C]butyric acid, polarization levels of 12.1 +/- 1.1% for AKV and 12.9 +/- 1.7% for AKB were achieved. Hyperpolarized [1-13C]butyrate metabolism in the heart revealed label incorporation into [1-13C]acetylcarnitine, [1-13C]acetoacetate, [1-13C]butyrylcarnitine, [5-13C]glutamate and [5-13C]citrate. This study demonstrates the potential of AKV and AKB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications.
Magnetic Resonance Imaging (MRI) of hard biological tissues is challenging due to the fleeting lifetime and low strength of their response to resonant stimuli, especially at low magnetic fields. Consequently, the impact of MRI on some medical applications, such as dentistry, continues to be limited. Here, we present three-dimensional reconstructions of ex-vivo human teeth, as well as a rabbit head and part of a cow femur, all obtained at a field strength of only 260 mT. These images are the first featuring soft and hard tissues simultaneously at sub-Tesla fields, and they have been acquired in a home-made, special-purpose, pre-medical MRI scanner designed with the goal of demonstrating dental imaging at low field settings. We encode spatial information with two variations of zero-echo time (ZTE) pulse sequences: Pointwise-Encoding Time reduction with Radial Acquisition (PETRA) and a new sequence we have called Double Radial Non-Stop Spin Echo (DRaNSSE), which we find to perform better than the former. For image reconstruction we employ Algebraic Reconstruction Techniques (ART) as well as standard Fourier methods. A noise analysis of the resulting images shows that ART reconstructions exhibit a higher signal to noise ratio with a more homogeneous noise distribution.
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