Fraser Robb

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate.

Metabolic imaging with hyperpolarized pyruvate was used to safely and noninvasively visualize prostate tumors in patients. The Hyperpolarized Prostate Cancer cells have a different metabolism than healthy cells. Specifically, they consume more pyruvate—a key component in glycolysis—than their normal counterparts. Nelson and colleagues therefore used a hyperpolarized form of pyruvate ([1-13C]pyruvate) to sensitively image increased levels of its product, [1-13C]lactate, as well as the flux of pyruvate to lactate. The [1-13C]pyruvate agent was used here in a first-in-human study in men with prostate cancer. Patients received varying doses of [1-13C]pyruvate that were found to be safe. These patients were then rapidly imaged with hyperpolarized 13C magnetic resonance (MR), which was able to provide dynamic (time course) information as well as three-dimensional (3D) (spatial) data at a single time point. Tumors were detected in all patients with biopsy-proven cancer. And, importantly, with 13C MR imaging (MRI), Nelson et al. were able to see cancer in regions of the prostate that were previously considered to be tumor-free upon inspection with other conventional anatomic imaging methods. With the ability to safely image tumor location and also follow tumor metabolism over time, hyperpolarized 13C MRI may be useful both for initial diagnosis and for monitoring therapy. Although the patients in this study had early-stage disease, the authors believe that [1-13C]lactate/[1-13C]pyruvate flux will only increase with tumor grade, making this imaging technology amenable to more advanced and aggressive cancers. Future studies will focus on optimizing agent preparation and delivery to ensure that this imaging technology can benefit patients in all clinical settings. This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate 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 [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate 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 [1-13C]pyruvate. 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 [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.

Clinical performance of contrast enhanced abdominal pediatric MRI with fast combined parallel imaging compressed sensing reconstruction

To deploy clinically, a combined parallel imaging compressed sensing method with coil compression that achieves a rapid image reconstruction, and assess its clinical performance in contrast‐enhanced abdominal pediatric MRI.

Multi-Channel Metabolic Imaging, with SENSE reconstruction, of Hyperpolarized [1-13C] Pyruvate in a Live Rat at 3.0 tesla on a Clinical MR Scanner

We report metabolic images of (13)C, following injection of a bolus of hyperpolarized [1-(13)C] pyruvate in a live rat. The data were acquired on a clinical scanner, using custom coils for volume transmission and array reception. Proton blocking of all carbon resonators enabled proton anatomic imaging with the system body coil, to allow for registration of anatomic and metabolic images, for which good correlation was achieved, with some anatomic features (kidney and heart) clearly visible in a carbon image, without reference to the corresponding proton image. Parallel imaging with sensitivity encoding was used to increase the spatial resolution in the SI direction of the rat. The signal to noise ratio in was in some instances unexpectedly high in the parallel images; variability of the polarization among different trials, plus partial volume effects, are noted as a possible cause of this.

A comparison of quantitative methods for clinical imaging with hyperpolarized 13C-pyruvate

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized 13C‐labelled molecules, such as the conversion of [1‐13C]pyruvate to [1‐13C]lactate, to be dynamically and non‐invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model‐free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two‐way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time‐to‐peak and the lactate‐to‐pyruvate area under the curve ratio were simple model‐free approaches that accurately represented the full reaction, with the time‐to‐peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized 13C data.

Dynamic Hyperpolarized Carbon-13 MR Metabolic Imaging of Nonhuman Primate Brain

To investigate hyperpolarized 13C metabolic imaging methods in the primate brain that can be translated into future clinical trials for patients with brain cancer.

Recent developments in combining LODESR imaging with proton NMR imaging

We have designed and constructed RF coil assemblies and the appropriate instrumentation for combining proton NMR imaging with LODESR imaging. This has enabled us to collect sequential images from the same sample using both methods. The coil assembly consists of a crossed ellipse coil for LODESR and proton NMR signal detection and a saddle coil for excitation of the ESR resonance. Images have been collected of phantoms containing copper sulphate and Tempol solutions. NMR images were collected (4.3 min) and within 30 s LODESR data collection started (collection time 2.5 min). Only the Tempol solutions are visible in the LODESR images.

Custom-Fitted 16-Channel Bilateral Breast Coil for Bidirectional Parallel Imaging

A 16‐channel receive‐only, closely fitted array coil is described and tested in vivo for bilateral breast imaging at 3 T. The primary purpose of this coil is to provide high signal‐to‐noise ratio and parallel imaging acceleration in two directions for breast MRI. Circular coil elements (7.5‐cm diameter) were placed on a closed “cup‐shaped” platform, and nearest neighbor coils were decoupled through geometric overlap. Comparisons were made between the 16‐channel custom coil and a commercially available 8‐channel coil. SENSitivity Encoding (SENSE) parallel imaging noise amplification (g‐factor) was evaluated in phantom scans. In healthy volunteers, we compared signal‐to‐noise ratio, parallel imaging in one and two directions, Autocalibrating Reconstruction for Cartesian sampling (ARC) g‐factor, and high spatial resolution imaging. When compared with a commercially available 8‐channel coil, the 16‐channel custom coil shows 3.6× higher mean signal‐to‐noise ratio in the breast and higher quality accelerated images. In patients, the 16‐channel custom coil has facilitated high‐quality, high‐resolution images with bidirectional acceleration of R = 6.3. Magn Reson Med, 2011.

Combined parallel and partial fourier MR reconstruction for accelerated 8-channel hyperpolarized carbon-13 in vivo magnetic resonance Spectroscopic imaging (MRSI).

To implement and evaluate combined parallel magnetic resonance imaging (MRI) and partial Fourier acquisition and reconstruction for rapid hyperpolarized carbon‐13 (13C) spectroscopic imaging. Short acquisition times mitigate hyperpolarized signal losses that occur due to T1 decay, metabolism, and radiofrequency (RF) saturation. Human applications additionally require rapid imaging to permit breath‐holding and to minimize the effects of physiologic motion.

Pregnant women models analyzed for RF exposure and temperature increase in 3T RF shimmed birdcages

MRI is increasingly used to scan pregnant patients. We investigated the effect of 3 Tesla (T) two‐port radiofrequency (RF) shimming in anatomical pregnant women models.

A semiflexible 64-channel receive-only phased array for pediatric body MRI at 3T.

To design, construct, and validate a semiflexible 64‐channel receive‐only phased array for pediatric body MRI at 3T.