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Open Access Publications from the University of California

Scholarly Works (17 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2019)

Magnetic resonance imaging with hyperpolarized 13C-labeled compounds via dynamic nuclear polarization (DNP) has been used to non-invasively study metabolic processes in vivo. This method provides a transient signal enhancement of more than 10,000 fold compared to imaging 13C compounds at thermal equilibrium. However, as soon as the pre-polarized 13C-labeled compound leaves the polarizer, its hyperpolarized state would irreversibly decay to the thermal equilibrium with a decay constant characterized by T1, which is typically less than one minute. The rapid loss of nonrenewable polarization brings challenges in hyperpolarized 13C magnetic resonance imaging. This dissertation presents improved acquisition methods for hyperpolarized 13C imaging with the injection of hyperpolarized [1-13C]pyruvate, which is the most widely studied substrate to date. The improved acquisition methods include a regional bolus tracking sequence for automatic acquisition timing, real-time calibration of frequency and RF power for more robust acquisitions, metabolite specific balanced steady state free precession (bSSFP) sequence and metabolite specific fast spin echo sequence for efficient use of polarization in hyperpolarized [1-13C] imaging. The proposed acquisition methods have been demonstrated in various clinical applications on a MR 3T scanner. Bolus tracking and real-time acquisition methods have been used in imaging human brain, heart, kidney and prostate. Metabolite specific bSSFP sequence has been applied in imaging human kidney. Metabolite specific fast spin echo sequence has been demonstrated in imaging human brain.

    Cover page: Improved Acquisition Methods for Hyperpolarized Carbon-13 Magnetic Resonance Imaging
    • Thesis
    • Peer Reviewed
    UC San Francisco Electronic Theses and Dissertations (2013)

    Hyperpolarization of metabolically active compounds labeled with 13C has been recently utilized for imaging metabolic processes in vivo. This work focused on developing a new 2D radiofrequency (RF) pulse for tracking a 13C-labeled pyruvate bolus injection in vivo. This pulse was designed for a clinical scanner, which allows for rapid translation to human studies. To meet clinical needs, we examined the flexibility of our design, and specifically the ability to shift the pulse location. The off-resonance response due to inhomogeneity, [1-13C]alanine and [1-13C]lactate have also been examined. Experimental results have validated the profile of our designed 2D RF pulse and off-resonance signals. To prepare for in vivo studies, our proposed pulse has been incorporated into a hyperpolarized 13C imaging sequence.

      Cover page: Development of a Novel 2D RF Pulse Sequence to Achieve An Improved Localization of Hyperpolarized <sup>13</sup>C Imaging
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2018)
      PURPOSE:Recent nuclear magnetic resonance and MRI studies have measured a fast-relaxing signal component with T2∗<1 ms in white matter and myelin extracts. In ex vivo studies, evidence suggests that a large fraction of this component directly arises from bound protons in the myelin phospholipid membranes. Based on these results, this ultrashort-T2 component in nervous tissue is a new potential imaging biomarker of myelination, which plays a critical role in neuronal signal conduction across the brain and loss or degradation of myelin is a key feature of many neurological disorders. The goal of this work was to characterize the relaxation times and frequency shifts of ultrashort-T2 components in the human brain. METHODS:This required development of an ultrashort echo time relaxometry acquisition strategy and fitting procedure for robust measurements in the presence of ultrashort T2∗ relaxation times and large frequency shifts. RESULTS:We measured an ultrashort-T2 component in healthy volunteers with a median T2∗ between 0.5-0.7 ms at 3T and 0.2-0.3 ms at 7T as well as an approximately -3 ppm frequency shift from water. CONCLUSION:To our knowledge, this is the first time a chemical shift of the ultrashort-T2 brain component has been measured in vivo. This chemical shift, at around 1.7 ppm, is similar to the primary resonance of most lipids, indicating that much of the ultrashort-T2 component observed in vivo arises from bound protons in the myelin phospholipid membranes. Magn Reson Med 80:726-735, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
        Cover page: In vivo characterization of brain ultrashort‐T2 components
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2015)

        Purpose

        A novel application of two-dimensional (2D) spatially selective radiofrequency (2DRF) excitation pulses in hyperpolarized 13C imaging is proposed for monitoring the bolus injection with highly efficient sampling of the initially polarized substrate, thus leaving more polarization available for detection of the subsequently generated metabolic products.

        Methods

        A 2DRF pulse was designed with a spiral trajectory and conventional clinical gradient performance. To demonstrate the ability of our 2DRF bolus tracking pulse sequence, hyperpolarized [1-(13)ruvate in vivo imaging experiments were performed in normal rats, with a comparison to 1DRF excitation pulses.

        Results

        Our designed 2DRF pulse was able to rapidly and efficiently monitor the injected bolus dynamics in vivo, with an 8-fold enhanced time resolution in comparison with 1DRF in our experimental settings. When applied at the pyruvate frequency for bolus tracking, our 2DRF pulse demonstrated reduced saturation of the hyperpolarization for the substrate and metabolic products compared to a 1DRF pulse, while being immune to ±0.5 ppm magnetic field inhomogeneity at 3T.

        Conclusion

        2DRF pulses in hyperpolarized 13C imaging can be used to efficiently monitor the bolus injection with reduced hyperpolarization saturation compared to 1DRF pulses. The parameters of our design are based on clinical scanner limits, which allows for rapid translation to human studies.
          Cover page: A 2DRF pulse sequence for bolus tracking in hyperpolarized 13C imaging
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2019)

          Purpose

          Acquisition timing and B1 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 B1 mapping and real-time B1 calibration based on regional B1 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 B1 scaling factors agreed with real-time acquired B1 maps. Flip angle correction using B1 maps results in a more consistent quantification of metabolic activity (i.e, pyruvate-to-lactate conversion, kPL ). Experiment recordings are provided to demonstrate the real-time actions during the experiment.

          Conclusions

          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.
            Cover page: A regional bolus tracking and real‐time B1 calibration method for hyperpolarized 13C MRI
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2019)

            Purpose

            Acquisition timing and B1 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 B1 mapping and real-time B1 calibration based on regional B1 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 B1 scaling factors agreed with real-time acquired B1 maps. Flip angle correction using B1 maps results in a more consistent quantification of metabolic activity (i.e, pyruvate-to-lactate conversion, kPL ). Experiment recordings are provided to demonstrate the real-time actions during the experiment.

            Conclusions

            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.
              Cover page: A regional bolus tracking and real-time B<sub>1</sub> calibration method for hyperpolarized <sup>13</sup> C MRI.
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2023)
              13C-bicarbonate is a crucial measure of pyruvate oxidation and TCA cycle flux, but is challenging to measure due to its relatively low concentration and thus will greatly benefit from improved signal-to-noise ratio (SNR). To address this, we developed and investigated the feasibility of a 3D stack-of-spirals metabolite-specific balanced steady-state free precession (MS-bSSFP) sequence for improving the SNR and spatial resolution of dynamic 13C-bicarbonate imaging in hyperpolarized [1-13C]pyruvate studies. The bicarbonate MS-bSSFP sequence was evaluated by simulations, phantoms studies, preclinical studies on five rats, brain studies on two healthy volunteers and renal study on one renal cell carcinoma patient. The simulations and phantom results showed that the bicarbonate-specific pulse had minimal perturbation of other metabolites (<1%). In the animal studies, the MS-bSSFP sequence provided an approximately 2.6-3 × improvement in 13C-bicarbonate SNR compared to a metabolite-specific gradient echo (MS-GRE) sequence without altering the bicarbonate or pyruvate kinetics, and the shorter spiral readout in the MS-bSSFP approach reduced blurring. Using the SNR ratio between MS-bSSFP and MS-GRE, the T2 values of bicarbonate and lactate in the rat kidneys were estimated as 0.5 s and 1.1 s, respectively. The in-vivo feasibility of bicarbonate MS-bSSFP sequence was demonstrated in two human brain studies and one renal study. These studies demonstrate the potential of the sequence for in-vivo applications, laying the foundation for future studies to observe this relatively low concentration metabolite with high-quality images and improve measurements of pyruvate oxidation.
                Cover page: A metabolite specific 3D stack-of-spirals bSSFP sequence for improved bicarbonate imaging in hyperpolarized [1-13C]Pyruvate MRI
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2020)

                Purpose

                The balanced steady-state free precession sequence has been previously explored to improve the efficient use of nonrecoverable hyperpolarized 13C 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 13C 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.
                  Cover page: A metabolite‐specific 3D stack‐of‐spiral bSSFP sequence for improved lactate imaging in hyperpolarized [1‐13C]pyruvate studies on a 3T clinical scanner
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2023)

                  Background

                  The heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy.

                  Methods

                  We developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load).

                  Results

                  We demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant.

                  Conclusions

                  We demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity.
                    Cover page: Regional quantification of cardiac metabolism with hyperpolarized [1-13C]-pyruvate CMR evaluated in an oral glucose challengeCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2020)

                    Purpose

                    The balanced steady-state free precession sequence has been previously explored to improve the efficient use of nonrecoverable hyperpolarized 13C 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 13C 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.
                      Cover page: A metabolite‐specific 3D stack‐of‐spiral bSSFP sequence for improved lactate imaging in hyperpolarized [1‐13C]pyruvate studies on a 3T clinical scanner
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