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Open Access Publications from the University of California

Scholarly Works (33 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2008)

Key engineering challenges associated with realizing the full potential of high field MRI are the design of phased array RF coils, the development of parallel imaging techniques for rapid imaging, and the determination of optimal acquisition parameters for various clinical applications. Parallel imaging techniques, which are enabled by phased array RF coils, take advantage of higher MRI field strengths by trading the higher SNR for imaging speed. I constructed a novel eight-channel non-overlapping phased array RF coil with capacitive decoupling for imaging of the brain and the hip, which was designed to minimize reconstruction-related SNR losses in parallel imaging. The design was aided by high frequency electromagnetic simulations that I programmed, and the coil was tested in various clinical applications, demonstrating quantitative performance improvements over a commercial eight-channel head coil. Higher field strengths improve the capability of intracranial time-of-flight MR angiography, an important fully non-invasive angiographic technique, due to the higher baseline SNR and the improved background suppression that is a result of longer T1 relaxation times. I optimized the acquisition protocol for 7T intracranial MRA, relying on a combination of simulations and experiments, and quantitatively verified the performance improvements over 3T. Using GRAPPA-based parallel imaging acquisition and reconstruction techniques that I developed, I designed a very high resolution (0.146mm3) protocol for 7T imaging of volunteers and patients with vascular disease. These techniques produced angiograms free from artifacts in all subjects, and correctly identified vascular pathology in patients.

    Cover page: Hardware and software developments for high field (>=3T) MRI
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2014)
    In this work we demonstrate for the first time directly detected manganese-55 ((55)Mn) magnetic resonance imaging (MRI) using a clinical 3T MRI scanner designed for human hyperpolarized (13)C clinical studies with no additional hardware modifications. Due to the similar frequency of the (55)Mn and (13)C resonances, the use of aqueous permanganate for large, signal-dense, and cost-effective "(13)C" MRI phantoms was investigated, addressing the clear need for new phantoms for these studies. Due to 100% natural abundance, higher intrinsic sensitivity, and favorable relaxation properties, (55)Mn MRI of aqueous permanganate demonstrates dramatically increased sensitivity over typical (13)C phantom MRI, at greatly reduced cost as compared with large (13)C-enriched phantoms. A large sensitivity advantage (22-fold) was demonstrated. A cylindrical phantom (d=8 cm) containing concentrated aqueous sodium permanganate (2.7 M) was scanned rapidly by (55)Mn MRI in a human head coil tuned for (13)C, using a balanced steady state free precession acquisition. The requisite penetration of radiofrequency magnetic fields into concentrated permanganate was investigated by experiments and high frequency electromagnetic simulations, and found to be sufficient for (55)Mn MRI with reasonably sized phantoms. A sub-second slice-selective acquisition yielded mean image signal-to-noise ratio of ~60 at 0.5 cm(3) spatial resolution, distributed with minimum central signal ~40% of the maximum edge signal. We anticipate that permanganate phantoms will be very useful for testing HP (13)C coils and methods designed for human studies.
      Cover page: Directly detected 55Mn MRI: Application to phantoms for human hyperpolarized 13C MRI development
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2018)
      PURPOSE: The bSSFP acquisition enables high spatiotemporal resolution for hyperpolarized 13C MRI at 3T, but is limited by spectral contamination from adjacent resonances. The purpose of this study was to develop a framework for in vivo dynamic high resolution imaging of hyperpolarized [1-13C]pyruvate and [1-13C]lactate generated in vivo at 3T by simplifying the spectrum through the use of selective suppression pulses. METHODS: Spectral suppression pulses were incorporated into the bSSFP sequence for suppression of [1-13C]alanine and [1-13C]pyruvate-hydrate signals, leaving only the pyruvate and lactate resonances. Subsequently, the bSSFP pulse width, time-bandwidth, and repetition time were optimized for imaging these dual resonances. RESULTS: The spectral suppression reduced both the alanine and pyruvate-hydrate signals by 85.5 ± 4.9% and had no significant effect on quantitation of pyruvate to lactate conversion (liver: P = 0.400, kidney: P = 0.499). High resolution (2 × 2 mm2 and 3 × 3 mm2) sub-second 2D coronal projections and 3D 2.5 mm isotropic images were obtained in rats and tumor-bearing mice with 1.8-5 s temporal resolution, allowing for calculation of lactate-to-pyruvate ratios and kPL. CONCLUSION: The developed framework presented here shows the capability for dynamic high resolution volumetric hyperpolarized bSSFP imaging of pyruvate-to-lactate conversion on a clinical 3T MR scanner.
        Cover page: High spatiotemporal resolution bSSFP imaging of hyperpolarized [1‐13C]pyruvate and [1‐13C]lactate with spectral suppression of alanine and pyruvate‐hydrate
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2016)

        Purpose

        The purpose of this study was to investigate (13) C hyperpolarization of α-ketobutyrate (αKB), an endogenous molecular analog of pyruvate, and its in vivo enzymatic conversion via lactate dehydrogenase (LDH) using localized MR spectroscopy.

        Methods

        Hyperpolarized (HP) (13) C MR experiments were conducted using [(13) C]αKB with rats in vivo and with isolated LDH enzyme in vitro, along with comparative experiments using [(13) C]pyruvate. Based on differences in the kinetics of its reaction with individual LDH isoforms, HP [(13) C]αKB was investigated as a novel MR probe, with added specificity for activity of LDHB-expressed H ("heart"-type) subunits of LDH (e.g., constituents of LDH-1 isoform).

        Results

        Comparable T1 and polarization values to pyruvate were attained (T1  = 52 s at 3 tesla [T], polarization = 10%, at C1 ). MR experiments showed rapid enzymatic conversion with substantially increased specificity. Formation of product HP [(13) C]α-hydroxybutyrate (αHB) from αKB in vivo was increased 2.7-fold in cardiac slabs relative to liver and kidney slabs. In vitro studies resulted in 5.0-fold higher product production from αKB with bovine heart LDH-1, as compared with pyruvate.

        Conclusions

        HP [(13) C]αKB may be a useful MR probe of cardiac metabolism and other applications where the role of H subunits of LDH is significant (e.g., renal cortex and brain).
          Cover page: Hyperpolarized [13C]ketobutyrate, a molecular analog of pyruvate with modified specificity for LDH isoforms
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2014)
          The accurate detection and characterization of cancerous tissue is still a major problem for the clinical management of individual cancer patients and for monitoring their response to therapy. MRI with hyperpolarized agents is a promising technique for cancer characterization because it can non-invasively provide a local assessment of the tissue metabolic profile. In this work, we measured the kinetics of hyperpolarized [1-(13)C] pyruvate and (13)C-urea in prostate and liver tumor models using a compressed sensing dynamic MRSI method. A kinetic model fitting method was developed that incorporated arbitrary RF flip angle excitation and measured a pyruvate to lactate conversion rate, Kpl, of 0.050 and 0.052 (1/s) in prostate and liver tumors, respectively, which was significantly higher than Kpl in healthy tissues [Kpl =0.028 (1/s), P<0.001]. Kpl was highly correlated to the total lactate to total pyruvate signal ratio (correlation coefficient =0.95). We additionally characterized the total pyruvate and urea perfusion, as in cancerous tissue there is both existing vasculature and neovascularization as different kinds of lesions surpass the normal blood supply, including small circulation disturbance in some of the abnormal vessels. A significantly higher perfusion of pyruvate (accounting for conversion to lactate and alanine) relative to urea perfusion was seen in cancerous tissues (liver cancer and prostate cancer) compared to healthy tissues (P<0.001), presumably due to high pyruvate uptake in tumors.
            Cover page: Kinetic and perfusion modeling of hyperpolarized 13 C pyruvate and urea in cancer with arbitrary RF flip angles
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2018)
            Acceleration of dynamic 2D (T2 Mapping) and 3D hyperpolarized 13C MRI acquisitions using the balanced steady-state free precession sequence was achieved with a specialized reconstruction method, based on the combination of low rank plus sparse and local low rank reconstructions. Methods were validated using both retrospectively and prospectively undersampled in vivo data from normal rats and tumor-bearing mice. Four-fold acceleration of 1-2 mm isotropic 3D dynamic acquisitions with 2-5 s temporal resolution and two-fold acceleration of 0.25-1 mm2 2D dynamic acquisitions was achieved. This enabled visualization of the biodistribution of [2-13C]pyruvate, [1-13C]lactate, [13C, 15N2]urea, and HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of high resolution T2 maps.
              Cover page: Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized 13C imaging using the bSSFP sequence
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2013)
              Metabolic imaging of hyperpolarized [1-(13)C] pyruvate co-polarized with [(13)C]urea by dynamic nuclear polarization with rapid dissolution is a promising new method for assessing tumor metabolism and perfusion simultaneously in vivo. Novel pulse sequences are required to enable dynamic imaging of multiple (13)C spectral lines with high spatiotemporal resolution. The goal of this study was to investigate a new frequency-specific approach for rapid metabolic imaging of multiple (13)C resonances using the spectral selectivity of steady-state free precession pulse (SSFP) trains. Methods developed in simulations were implemented in a dynamic frequency-cycled balanced SSFP pulse sequence on a 14.1-T animal magnetic resonance imaging scanner. This acquisition was tested in thermal and hyperpolarized phantom imaging studies and in a transgenic mouse with prostate cancer.
                Cover page: Frequency-specific SSFP for hyperpolarized 13C metabolic imaging at 14.1 T
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2014)

                Purpose

                To demonstrate simultaneous hyperpolarization and imaging of three (13)C-labeled perfusion MRI contrast agents with dissimilar molecular structures ([(13)C]urea, [(13)C]hydroxymethyl cyclopropane, and [(13)C]t-butanol) and correspondingly variable chemical shifts and physiological characteristics, and to exploit their varying diffusibility for simultaneous measurement of vascular permeability and perfusion in initial preclinical studies.

                Methods

                Rapid and efficient dynamic multislice imaging was enabled by a novel pulse sequence incorporating balanced steady state free precession excitation and spectral-spatial readout by multiband frequency encoding, designed for the wide, regular spectral separation of these compounds. We exploited the varying bilayer permeability of these tracers to quantify vascular permeability and perfusion parameters simultaneously, using perfusion modeling methods that were investigated in simulations. "Tripolarized" perfusion MRI methods were applied to initial preclinical studies with differential conditions of vascular permeability, in normal mouse tissues and advanced transgenic mouse prostate tumors.

                Results

                Dynamic imaging revealed clear differences among the individual tracer distributions. Computed permeability maps demonstrated differential permeability of brain tissue among the tracers, and tumor perfusion and permeability were both elevated over values expected for normal tissues.

                Conclusion

                Tripolarized perfusion MRI provides new molecular imaging measures for specifically monitoring permeability, perfusion, and transport simultaneously in vivo.
                  Cover page: Simultaneous multiagent hyperpolarized 13C perfusion imaging
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2017)

                  Purpose

                  Dissolution dynamic nuclear polarization (DNP) enables the acquisition of 13 C magnetic resonance data with a high sensitivity. Recently, metabolically inactive hyperpolarized 13 C-labeled compounds have shown to be potentially useful for perfusion imaging. The purpose of this study was to validate hyperpolarized perfusion imaging methods by comparing with conventional gadolinium (Gd)-based perfusion MRI techniques and pathology.

                  Methods

                  Dynamic 13 C data using metabolically inactive hyperpolarized bis-1,1-(hydroxymethyl)-[1-13 C]cyclopropane-d8 (HMCP) were obtained from an orthotopic human glioblastoma (GBM) model for the characterization of tumor perfusion and compared with standard Gd-based dynamic susceptibility contrast (DSC) MRI data and immunohistochemical analysis from resected brains.

                  Results

                  Distinct HMCP perfusion characteristics were observed within the GBM tumors compared with contralateral normal brain tissue. The perfusion parameters obtained from the hyperpolarized HMCP data in tumor were strongly correlated with normalized peak height measured from the DSC images. The results from immunohistochemical analysis supported these findings by showing a high level of vascular staining for tumor that exhibited high levels of hyperpolarized HMCP signal.

                  Conclusion

                  The results from this study have demonstrated that hyperpolarized HMCP data can be used as an indicator of tumor perfusion in an orthotopic xenograft model for GBM. Magn Reson Med 77:841-847, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
                    Cover page: Investigating tumor perfusion by hyperpolarized 13C MRI with comparison to conventional gadolinium contrast‐enhanced MRI and pathology in orthotopic human GBM xenografts
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2016)

                    Purpose

                    Hyperpolarization of carbon-13 ((13) C) nuclei by dissolution dynamic nuclear polarization increases signal-to-noise ratio (SNR) by >10,000-fold for metabolic imaging, but care must be taken when transferring hyperpolarized (HP) samples from polarizer to MR scanner. Some (13) C substrates relax rapidly in low ambient magnetic fields. A handheld electromagnet carrier was designed and constructed to preserve polarization by maintaining a sufficient field during sample transfer.

                    Methods

                    The device was constructed with a solenoidal electromagnet, powered by a nonmagnetic battery, holding the HP sample during transfer. A specially designed switch automated deactivation of the field once transfer was complete. Phantom and rat experiments were performed to compare MR signal enhancement with or without the device for HP [(13) C]urea and [1-(13) C]pyruvate.

                    Results

                    The magnetic field generated by this device was tested to be >50 G over a 6-cm central section. In phantom and rat experiments, [(13) C]urea transported via the device showed SNR improvement by a factor of 1.8-1.9 over samples transferred through the background field.

                    Conclusion

                    A device was designed and built to provide a suitably high yet safe magnetic field to preserve hyperpolarization during sample transfer. Comparative testing demonstrated SNR improvements of approximately two-fold for [(13) C]urea while maintaining SNR for [1-(13) C]pyruvate.
                      Cover page: Handheld electromagnet carrier for transfer of hyperpolarized carbon‐13 samples
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