Investigating cerebral perfusion with high resolution hyperpolarized [1-13 C]pyruvate MRI.

PURPOSE: To investigate high-resolution hyperpolarized (HP) 13 C pyruvate MRI for measuring cerebral perfusion in the human brain. METHODS: HP [1-13 C]pyruvate MRI was acquired in five healthy volunteers with a multi-resolution EPI sequence with 7.5 × 7.5 mm2 resolution for pyruvate. Perfusion parameters were calculated from pyruvate MRI using block-circulant singular value decomposition and compared to relative cerebral blood flow calculated from arterial spin labeling (ASL). To examine regional perfusion patterns, correlations between pyruvate and ASL perfusion were performed for whole brain, gray matter, and white matter voxels. RESULTS: High resolution 7.5 × 7.5 mm2 pyruvate images were used to obtain relative cerebral blood flow (rCBF) values that were significantly positively correlated with ASL rCBF values (r = 0.48, 0.20, 0.28 for whole brain, gray matter, and white matter voxels respectively). Whole brain voxels exhibited the highest correlation between pyruvate and ASL perfusion, and there were distinct regional patterns of relatively high ASL and low pyruvate normalized rCBF found across subjects. CONCLUSION: Acquiring HP 13 C pyruvate metabolic images at higher resolution allows for finer spatial delineation of brain structures and can be used to obtain cerebral perfusion parameters. Pyruvate perfusion parameters were positively correlated to proton ASL perfusion values, indicating a relationship between the two perfusion measures. This HP 13 C study demonstrated that hyperpolarized pyruvate MRI can assess cerebral metabolism and perfusion within the same study.

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage.

Hyperpolarized (HP) 13C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-13C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire 13C-labeled volumetric and dynamic images of [2-13C]pyruvate and downstream metabolites [5-13C]glutamate and [2-13C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (kPL) and pyruvate-to-glutamate (kPG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.

Assessment of higher-order singular value decomposition denoising methods on dynamic hyperpolarized [1-13C]pyruvate MRI data from patients with glioma.

BACKGROUND: Real-time metabolic conversion of intravenously-injected hyperpolarized [1-13C]pyruvate to [1-13C]lactate and [13C]bicarbonate in the brain can be measured using dynamic hyperpolarized carbon-13 (HP-13C) MRI. However, voxel-wise evaluation of metabolism in patients with glioma is challenged by the limited signal-to-noise ratio (SNR) of downstream 13C metabolites, especially within lesions. The purpose of this study was to evaluate the ability of higher-order singular value decomposition (HOSVD) denoising methods to enhance dynamic HP [1-13C]pyruvate MRI data acquired from patients with glioma. METHODS: Dynamic HP-13C MRI were acquired from 14 patients with glioma. The effects of two HOSVD denoising techniques, tensor rank truncation-image enhancement (TRI) and global-local HOSVD (GL-HOSVD), on the SNR and kinetic modeling were analyzed in [1-13C]lactate data with simulated noise that matched the levels of [13C]bicarbonate signals. Both methods were then evaluated in patient data based on their ability to improve [1-13C]pyruvate, [1-13C]lactate and [13C]bicarbonate SNR. The effects of denoising on voxel-wise kinetic modeling of kPL and kPB was also evaluated. The number of voxels with reliable kinetic modeling of pyruvate-to-lactate (kPL) and pyruvate-to-bicarbonate (kPB) conversion rates within regions of interest (ROIs) before and after denoising was then compared. RESULTS: Both denoising methods improved metabolite SNR and regional signal coverage. In patient data, the average increase in peak dynamic metabolite SNR was 2-fold using TRI and 4-5 folds using GL-HOSVD denoising compared to acquired data. Denoising reduced kPL modeling errors from a native average of 23% to 16% (TRI) and 15% (GL-HOSVD); and kPB error from 42% to 34% (TRI) and 37% (GL-HOSVD) (values were averaged voxelwise over all datasets). In contrast-enhancing lesions, the average number of voxels demonstrating within-tolerance kPL modeling error relative to the total voxels increased from 48% in the original data to 84% (TRI) and 90% (GL-HOSVD), while the number of voxels showing within-tolerance kPB modeling error increased from 0% to 15% (TRI) and 8% (GL-HOSVD). CONCLUSION: Post-processing denoising methods significantly improved the SNR of dynamic HP-13C imaging data, resulting in a greater number of voxels satisfying minimum SNR criteria and maximum kinetic modeling errors in tumor lesions. This enhancement can aid in the voxel-wise analysis of HP-13C data and thereby improve monitoring of metabolic changes in patients with glioma following treatment.

Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism.

PURPOSE: To investigate multi-resolution hyperpolarized (HP) 13 C pyruvate MRI for measuring kinetic conversion rates in the human brain. METHODS: HP [1-13 C]pyruvate MRI was acquired in 6 subjects with a multi-resolution EPI sequence at 7.5 × 7.5 mm2 resolution for pyruvate and 15 × 15 mm2 resolution for lactate and bicarbonate. With the same lactate data, 2 quantitative maps of pyruvate-to-lactate conversion (kPL ) maps were generated: 1 using 7.5 × 7.5 mm2 resolution pyruvate data and the other using synthetic 15 × 15 mm2 resolution pyruvate data to simulate a standard constant resolution acquisition. To examine local kPL values, 4 voxels were manually selected in each study representing brain tissue near arteries, brain tissue near veins, white matter, and gray matter. RESULTS: High resolution 7.5 × 7.5 mm2 pyruvate images increased the spatial delineation of brain structures and decreased partial volume effects compared to coarser resolution 15 × 15 mm2 pyruvate images. Voxels near arteries, veins and in white matter exhibited higher calculated kPL for multi-resolution images. CONCLUSION: Acquiring HP 13 C pyruvate metabolic data with a multi-resolution approach minimized partial volume effects from vascular pyruvate signals while maintaining the SNR of downstream metabolites. Higher resolution pyruvate images for kinetic fitting resulted in increased kinetic rate values, particularly around the superior sagittal sinus and cerebral arteries, by reducing extracellular pyruvate signal contributions from adjacent blood vessels. This HP 13 C study showed that acquiring pyruvate with finer resolution improved the quantification of kinetic rates throughout the human brain.

Initial Experience on Hyperpolarized [1-13C]Pyruvate MRI Multicenter Reproducibility-Are Multicenter Trials Feasible?

BACKGROUND: Magnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate allows real-time and pathway specific clinical detection of otherwise unimageable in vivo metabolism. However, the comparability between sites and protocols is unknown. Here, we provide initial experiences on the agreement of hyperpolarized MRI between sites and protocols by repeated imaging of same healthy volunteers in Europe and the US. METHODS: Three healthy volunteers traveled for repeated multicenter brain MRI exams with hyperpolarized [1-13C]pyruvate within one year. First, multisite agreement was assessed with the same echo-planar imaging protocol at both sites. Then, this was compared to a variable resolution echo-planar imaging protocol. In total, 12 examinations were performed. Common metrics of 13C-pyruvate to 13C-lactate conversion were calculated, including the kPL, a model-based kinetic rate constant, and its model-free equivalents. Repeatability was evaluated with intraclass correlation coefficients (ICC) for absolute agreement computed using two-way random effects models. RESULTS: The mean kPL across all examinations in the multisite comparison was 0.024 ± 0.0016 s-1. The ICC of the kPL was 0.83 (p = 0.14) between sites and 0.7 (p = 0.09) between examinations of the same volunteer at any of the two sites. For the model-free metrics, the lactate Z-score had similar site-to-site ICC, while it was considerably lower for the lactate-to-pyruvate ratio. CONCLUSIONS: Estimation of metabolic conversion from hyperpolarized [1-13C]pyruvate to lactate using model-based metrics such as kPL suggests close agreement between sites and examinations in volunteers. Our initial results support harmonization of protocols, support multicenter studies, and inform their design.