The ability of hyperpolarized carbon-13 MR metabolic imaging to acquire dynamic metabolic information in real time is crucial to gain mechanistic insights into metabolic pathways, which are ...complementary to anatomic and other functional imaging methods. This review presents the advantages of this emerging functional imaging technology, describes considerations in clinical translations, and summarizes current human brain applications. Despite rapid development in methodologies, significant technological and physiological related challenges continue to impede broader clinical translation.
Double-tuned radio-frequency (RF) coils for heteronuclear mangentic resonance (MR) require sufficient electromagnetic isolation between the two resonators operating at two Larmor frequencies and ...independent tuning in order to attain highly efficient signal acquisition at each frequency. In this work, a novel method for double-tuned coil design at 7T based on the concept of common-mode differential-mode (CMDM) was developed and tested. Common mode (CM) and differential mode (DM) currents exist within two coupled parallel transmission lines, e.g., microstrip lines, yielding two different current distributions. The electromagnetic (EM) fields of the CM and DM are orthogonal to each other, and thus, the two modes are intrinsically EM decoupled. The modes can be tuned independently to desired frequencies, thus satisfying the requirement of dual-frequency MR applications. To demonstrate the feasibility and efficiency of the proposed CMDM technique, CMDM surface coils and volume coils using microstrip transmission line for 1 H and 13 C MRI/MRSI were designed, constructed, and tested at 7T. Bench test results showed that the isolations between the two frequency channels of the CMDM surface coil and volume coil were better than -30 and -25 dB, respectively. High quality MR phantom images were also obtained using the CMDM coils. The performance of the CMDM technique was validated through a comparison with the conventional two-pole design method at 7T. The proposed CMDM technique can be also implemented by using other coil techniques such as lumped element method, and can be applied to designing double-tuned parallel imaging coil arrays. Furthermore, if the two resonant modes of a CMDM coil were tuned to the same frequency, the CMDM coil becomes a quadrature coil due to the intrinsic orthogonal field distribution of CM and DM.
This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized 1-¹³Cpyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with ...prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo ¹³C MR data, it is possible to evaluate the distribution of agents such as 1-¹³Cpyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized 1-¹³Clactate in tumor, with the ratio of 1-¹³Clactate/1-¹³Cpyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect ¹³C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized 1-¹³Cpyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized 1-¹³Cpyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated 1-¹³Clactate/1-¹³Cpyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.
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 as13 C or15 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.
Zero- to ultralow-field (ZULF) nuclear magnetic resonance (NMR) is an emerging tool for precision chemical analysis. In this work, we study dynamic processes and investigate the influence of chemical ...exchange on ZULF NMR J-spectra. We develop a computational approach that allows quantitative calculation of J-spectra in the presence of chemical exchange and apply it to study aqueous solutions of
Nammonium (
NFormula: see text) as a model system. We show that pH-dependent chemical exchange substantially affects the J-spectra and, in some cases, can lead to degradation and complete disappearance of the spectral features. To demonstrate potential applications of ZULF NMR for chemistry and biomedicine, we show a ZULF NMR spectrum of 2-
Cpyruvic acid hyperpolarized via dissolution dynamic nuclear polarization (dDNP). We foresee applications of affordable and scalable ZULF NMR coupled with hyperpolarization to study chemical exchange phenomena in vivo and in situations where high-field NMR detection is not possible to implement.
Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR ...scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good‐quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi‐adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.
![Hyperpolarized 1-[13C]-Pyru...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0302-2838_1421-993X_1873-7560/small "Hyperpolarized 1-[13C]-Pyruvate Magnetic Resonance Imaging Detects an Early Metabolic Response to Androgen Ablation Therapy in Prostate Cancer")
PDF
