Biomedical applications of the dynamic nuclear polarization and parahydrogen induced polarization techniques for hyperpolarized 13C MR imaging

Since the first pioneering report of hyperpolarized [1-13C]pyruvate magnetic resonance imaging (MRI) of the Warburg effect in prostate cancer patients, clinical dissemination of the technique has been rapid; close to 10 sites worldwide now possess a polarizer fit for the clinic, and more than 30 clinical trials, predominantly for oncological applications, are already registered on the US and European clinical trials databases. Hyperpolarized 13C probes to study pathophysiological processes beyond the Warburg effect, including tricarboxylic acid cycle metabolism, intra-cellular pH and cellular necrosis have also been demonstrated in the preclinical arena and are pending clinical translation, and the simultaneous injection of multiple co-polarized agents is opening the door to high-sensitivity, multi-functional molecular MRI with a single dose. Here, we review the biomedical applications to date of the two polarization methods that have been used for in vivo hyperpolarized 13C molecular MRI; namely, dissolution dynamic nuclear polarization and parahydrogen-induced polarization. The basic concept of hyperpolarization and the fundamental theory underpinning these two key 13C hyperpolarization methods, along with recent technological advances that have facilitated biomedical realization, are also covered

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession

Purpose To demonstrate the potential for high quality MRI of pulmonary ventilation using naturally abundant xenon (NAXe) gas. Methods MRI was performed at 1.5 Tesla (T) and 3 T on one healthy smoker and two healthy never-smokers. 129Xe gas was polarized to ∼25% using an in-house spin-exchange optical pumping polarizer fitted with a laser diode array with integrated volume holographic grating and optical train system. Volunteers inhaled 1 L of NAXe for an 8 to 15 s breathhold while MR images were acquired with full-lung coverage using a three-dimensional steady-state free precession sequence, optimized for maximum signal-to-noise ratio (SNR) at a given spatial resolution. For the purpose of image quality comparison, the MR acquisition was repeated at 1.5 T with 400 mL enriched xenon and 200 mL 3He. Results All NAXe lung images were of high quality, with mean SNRs of 25–40 (voxel 4.2 × 4.2 × 8/10 mm3) and ∼30% improvement at 3 T versus 1.5 T. The high SNR permitted identification of minor ventilation defects in the healthy smoker's lungs. NAXe images were of comparable SNR to those obtained with enriched xenon and 3He. Conclusion Optimization of MR pulse sequences and advances in polarization technology have facilitated high quality pulmonary ventilation imaging with inexpensive NAXe gas. Magn Reson Med 74:346–352, 2015

High resolution spectroscopy and chemical shift imaging of hyperpolarized 129 Xe dissolved in the human brain in vivo at 1.5 tesla

Purpose Upon inhalation, xenon diffuses into the bloodstream and is transported to the brain, where it dissolves in various compartments of the brain. Although up to five chemically distinct peaks have been previously observed in 129Xe rat head spectra, to date only three peaks have been reported in the human head. This study demonstrates high resolution spectroscopy and chemical shift imaging (CSI) of 129Xe dissolved in the human head at 1.5 Tesla. Methods A 129Xe radiofrequency coil was built in-house and 129Xe gas was polarized using spin-exchange optical pumping. Following the inhalation of 129Xe gas, NMR spectroscopy was performed with spectral resolution of 0.033 ppm. Two-dimensional CSI in all three anatomical planes was performed with spectral resolution of 2.1 ppm and voxel size 20 mm × 20 mm. Results Spectra of hyperpolarized 129Xe dissolved in the human head showed five distinct peaks at 188 ppm, 192 ppm, 196 ppm, 200 ppm, and 217 ppm. Assignment of these peaks was consistent with earlier studies. Conclusion High resolution spectroscopy and CSI of hyperpolarized 129Xe dissolved in the human head has been demonstrated. For the first time, five distinct NMR peaks have been observed in 129Xe spectra from the human head in vivo

Whole lung morphometry with 3D multiple b-value hyperpolarized gas MRI and compressed sensing.

PURPOSE: To demonstrate three-dimensional (3D) multiple b-value diffusion-weighted (DW) MRI of hyperpolarized (3) He gas for whole lung morphometry with compressed sensing (CS). METHODS: A fully-sampled, two b-value, 3D hyperpolarized (3) He DW-MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the ky and kz phase-encoding directions for CS simulations. Optimal k-space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully-sampled (3) He apparent diffusion coefficient (ADC) maps. Prospective three-fold, undersampled, 3D multiple b-value (3) He DW-MRI datasets were acquired from five healthy volunteers and one chronic obstructive pulmonary disease (COPD) patient, and the mean values of maps of ADC and mean alveolar dimension (LmD ) were validated against two-dimensional (2D) and 3D fully-sampled (3) He DW-MRI experiments. RESULTS: Reconstructed undersampled datasets showed no visual artifacts and good preservation of the main image features and quantitative information. A good agreement between fully-sampled and prospective undersampled datasets was found, with a mean difference of +3.4% and +5.1% observed in mean global ADC and LmD values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs. CONCLUSIONS: Accelerated CS acquisition has facilitated 3D multiple b-value (3) He DW-MRI scans in a single breath-hold, enabling whole lung morphometry mapping. Magn Reson Med, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Long-range heteronuclear J-coupling constants in esters: Implications for 13C metabolic MRI by side-arm parahydrogen-induced polarization

Side-arm parahydrogen induced polarization (PHIP-SAH) presents a cost-effective method for hyperpolarization of 13C metabolites (e.g. acetate, pyruvate) for metabolic MRI. The timing and efficiency of typical spin order transfer methods including magnetic field cycling and tailored RF pulse sequences crucially depends on the heteronuclear J coupling network between nascent parahydrogen protons and 13C, post-parahydrogenation of the target compound. In this work, heteronuclear nJHC (1 < n ≤ 5) couplings of acetate and pyruvate esters pertinent for PHIP-SAH were investigated experimentally using selective HSQMBC-based pulse sequences and numerically using DFT simulations. The CLIP-HSQMBC technique was used to quantify 2/3-bond JHC couplings, and 4/5-bond JHC ≲ 0.5 Hz were estimated by the sel-HSQMBC-TOCSY approach. Experimental and numerical (DFT-simulated) nJHC couplings were strongly correlated (P < 0.001). Implications for 13C hyperpolarization by magnetic field cycling, and PH-INEPT and ESOTHERIC type spin order transfer methods for PHIP-SAH were assessed, and the influence of direct nascent parahydrogen proton to 13C coupling when compared with indirect homonuclear TOCSY-type transfer through intermediate (non-nascent parahydrogen) protons was studied by the density matrix approach

Simultaneous T2* mapping of 14N- and 15N-labeled dicarboxy-PROXYLs using CW-EPR-based single-point imaging

This article reports a method of simultaneous T2* mapping of 14N- and 15N-labeled dicarboxy-PROXYLs using 750-MHz continuous-wave electron paramagnetic resonance (CW-EPR) imaging. To separate the spectra of 14N- and 15N-labeled dicarboxy-PROXYLs under magnetic field gradients, an optimization problem for spectral projections was formulated with the spatial total variation as a regularization term and solved using a local search based on the gradient descent algorithm. Using the single-point imaging (SPI) method with spectral projections of each radical, simultaneous T2* mapping was performed for solution samples. Simultaneous T2* mapping enabled visualization of the response of T2* values to the level of dissolved oxygen in the solution. Simultaneous T2* mapping applied to a mouse tumor model demonstrated the feasibility of the reported method for potential application to in vivo oxygenation imaging

Reproducibility of quantitative indices of lung function and microstructure from 129Xe chemical shift saturation recovery (CSSR) MR spectroscopy

Purpose To evaluate the reproducibility of indices of lung microstructure and function derived from 129Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. Methods Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age-matched volunteers were scanned three times on one day, to assess reproducibility. Results CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P < 0.001; P = 0.057, respectively). Intra-subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 ± 1.9% and 6.0 ± 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole-lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 ± 8.0% and 18.0 ± 19.3%, respectively. Conclusion 129Xe CSSR presents a reproducible method for estimation of alveolar septal thickness

Multiple breath washout of hyperpolarized 129Xe and 3He in human lungs with 3D bSSFP imaging

Purpose: (i) To compare quantitative fractional ventilation measurements from multiple breath washout imaging (MBW-I) using hyperpolarized (HP) 3He with both spoiled gradient echo (SPGR) and balanced steady-state free-precession (bSSFP) 3D pulse sequences and (ii) to evaluate the feasibility of MBW-I with HP 129Xe. Methods: Seven healthy volunteers were scanned using 3He MBW-I with 3D SPGR and bSSFP sequences. Five also underwent MBW-I with 129Xe. A dual-tuned coil was used to acquire MBW-I data from both nuclei in the same subject position, enabling direct comparison of regional information. Results: High-quality MBW images were obtained with bSSFP sequences using a reduced dose (100ml) of inhaled hyperpolarized 3He. 3D MBW-I with 129Xe was also successfully demonstrated with a bSSFP sequence. Regional quantitative ventilation measures derived from 3He and 129Xe MBW-I correlated well in all subjects (p<0.001) with mean Pearson’s correlation coefficients of r=0.61 and r=0.52 for 3He SPGR-bSSFP and 129Xe-3He (bSSFP) comparisons. The average inter-volunteer mean difference (and standard deviation) in fractional ventilation in SPGR-bSSFP and 129Xe-3He comparisons was 15% (28%) and 9% (38%), respectively. Conclusions: Improved sensitivity in MBW-I can be achieved with polarization-efficient bSSFP sequences. Same scan-session 3D MBW-I with 3He and 129Xe has been demonstrated using a dual-tuned coil