This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall goal of this project is to develop a robust set of instrumentation and methods that facilitate the translation of new discoveries into powerful tools for cancer research and clinical cancer care. The ultimate potential of hyperpolarized (HP) agents is fully realized when these agents are used to probe molecular interactions of cancer in vivo. Small animal models of cancer play a crucial role in the evaluation and validation of novel diagnostic agents and in the discovery and optimization of new approaches to cancer therapy. Unfortunately, the constraints inherent to detection of HP agents are unique and the limited availability of polarizing systems to date has restricted the development of imaging technologies and instrumentation that are optimized for that purpose. Lack of such infrastructure, in turn, slows the demonstration of new applications in vivo and tempers the rate at which new discoveries can progress to clinical care. Significant opportunities currently exist to address these needs and influence the development of imaging technologies and instrumentation for HP measurements in both experimental and clinical settings. Klaes Golman first demonstrated metabolic imaging using HP 13C-labeled pyruvate in rats using a 1H/13C dual-tuned volume coil and a standard chemical-shift imaging (CSI) sequence with centric k-space encoding. Kevin Brindle's group at the Cambridge Research Institute has shown an early indication of response to therapy in the kinetics of HP-[1-13C]-pyruvate when measured using a standard CSI sequence and a surface coil (which aided signal localization) that was tuned to 13C. Scientists at UCSF and GE have developed an efficient double spin-echo echo-planar spectroscopic imaging (EPSI) sequence for HP-13C measurements and have applied compressed sensing to accelerate acquisitions made using a home-made 1H/13C dual-tuned volume coil. Leupold et al. have employed an iterative Dixon-like reconstruction to minimize encoding in the spectral domain for steady-state imaging of proton and HP-13C-CSI using a quadrature 13C surface coil. None but the most basic (and least efficient) of these sequences are widely available to researchers that seek to employ HP-13C methods in vivo, and only one of these groups has utilized a commercially available coil rather than purpose-built detectors that are tailored for specific experimental conditions. Notably absent from all of these approaches is the use of multichannel 13C capabilities to further accelerate data acquisition by parallel encoding. Increases in sensitivity and signal localization using arrays could lead to substantial improvements in spatial and temporal resolution when measuring HP-13C in vivo. This project leverages the expertise of colleagues at The University of Texas M.D. Anderson Cancer Center in imaging physics, experimental MRI, systems engineering, and small animal imaging for the development of coils, sequences, and reconstruction algorithms that are tailored to the unique constraints imposed by measurements of hyperpolarized media. Coils and arrays that are optimized and tailored for specific measurements will improve sensitivity and support efficient image acquisition methods. Fast and efficient pulse sequences will gather the most information from the decaying signal pool and improve spatial and temporal resolution. Acceleration via parallel imaging will further preserve signal by enabling reconstruction from fewer signal excitations and phase-encoding repetitions. Thorough characterization of coils and sequences will yield a robust platform for HP-CSI and provide a direct conduit for HP-CSI in small animal models of cancer. These goals will be achieved through three specific aims:
Aim 1 : Coils and arrays for quantitative MRSI of hyperpolarized nuclei.
This aim will ensure that science is not held hostage by lack of commercially available instrumentation. Coils that support proton and hyperpolarized nuclei will be optimized, characterized, and provided to partners in this Texas network. The capability of multinuclear arrays to further improve the quality and resolution of HP-CSI will be tested.
Aim 2 : Sequences for rapid and efficient encoding and reconstruction. Efficient signal encoding and rapid imaging sequences improve the spatial and temporal resolution at which measurements can be made from decaying signal.
This aim will focus on two classes of experiments: one for HP-13C observe, and one for rapid 1H imaging following polarization transfer (13C to 1H) in HP glucose analogues. Parallel and constrained image reconstruction methods will be integrated into rapid HP-CSI and HP-MRI sequences and their potential for acceleration will be tested.
Aim 3 : Integration of hyperpolarized measurements into preclinical cancer research. Optimized single-channel and parallel imaging methods for hyperpolarized experiments will be integrated into ongoing research involving small animal models of cancer at MDACC and UTSW, with provisions to increase study size and evaluate the repeatability of these methods.
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