A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as (13)C or (15)N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism-poor sensitivity-while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care.

This white paper discusses prospects for advancing hyperpolarization technology to better understand cancer metabolism, identify current obstacles to HP (hyperpolarized) 13C magnetic resonance imaging’s (MRI’s) widespread clinical use, and provide recommendations for overcoming them. Since the publication of the first NIH white paper on hyperpolarized 13C MRI in 2011, preclinical studies involving [1-13C]pyruvate as well a number of other 13C labeled metabolic substrates have demonstrated this technology's capacity to provide unique metabolic information. A dose-ranging study of HP [1-13C]pyruvate in patients with prostate cancer established safety and feasibility of this technique. Additional studies are ongoing in prostate, brain, breast, liver, cervical, and ovarian cancer. Technology for generating and delivering hyperpolarized agents has evolved, and new MR data acquisition sequences and improved MRI hardware have been developed. It will be important to continue investigation and development of existing and new probes in animal models. Improved polarization technology, efficient radiofrequency coils, and reliable pulse sequences are all important objectives to enable exploration of the technology in healthy control subjects and patient populations. It will be critical to determine how HP 13C MRI might fill existing needs in current clinical research and practice, and complement existing metabolic imaging modalities. Financial sponsorship and integration of academia, industry, and government efforts will be important factors in translating the technology for clinical research in oncology. This white paper is intended to provide recommendations with this goal in mind.

Differences in the LB/WB SAR ratios across testing labs and various MRI scanners could lead to inconsistent WB SAR labeling. Magnetic resonance (MR) conditional labeling based on WB SAR should be derived from a conservative estimate of global LB/WB ratios.

Patients with deep brain stimulation devices highly benefit from postoperative MRI exams, however MRI is not readily accessible to these patients due to safety risks associated with RF heating of the implants. Recently we introduced a patient-adjustable reconfigurable coil technology that substantially reduced local SAR at tips of single isolated DBS leads during MRI at 1.5 T in 9 realistic patient models. This contribution extends our work to higher fields by demonstrating the feasibility of scaling the technology to 3T and assessing its performance in patients with bilateral leads as well as fully implanted systems. We developed patient-derived models of bilateral DBS leads and fully implanted DBS systems from postoperative CT images of 13 patients and performed finite element simulations to calculate SAR amplification at electrode contacts during MRI with a reconfigurable rotating coil at 3T. Compared to a conventional quadrature body coil, the reconfigurable coil system reduced the SAR on average by 83% for unilateral leads and by 59% for bilateral leads. A simple surgical modification in trajectory of implanted leads was demonstrated to increase the SAR reduction efficiency of the rotating coil to >90% in a patient with a fully implanted bilateral DBS system. Thermal analysis of temperature-rise around electrode contacts during typical brain exams showed a 15-fold heating reduction using the rotating coil, generating <1 C temperature rise during~4-min imaging with high-SAR sequences where a conventional CP coil generated >10 C temperature rise in the tissue for the same flip angle.