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BackgroundMagnetic 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.MethodsThree 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.ResultsThe 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.ConclusionsEstimation 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.

Acute ischemic stroke patients benefit from reperfusion in a short time-window after debut. Later treatment may be indicated if viable brain tissue is demonstrated and this outweighs the inherent risks of late reperfusion. Magnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate is an emerging technology that directly images metabolism. Here, we investigated its potential to detect viable tissue in ischemic stroke. Stroke was induced in pigs by intracerebral injection of endothelin 1. During ischemia, the rate constant of pyruvate-to-lactate conversion, kPL, was 52% larger in penumbra and 85% larger in the infarct compared to the contralateral hemisphere (P = 0.0001). Within the penumbra, the kPL was 50% higher in the regions that later infarcted compared to non-progressing regions (P = 0.026). After reperfusion, measures of pyruvate-to-lactate conversion were slightly decreased in the infarct compared to contralateral. In addition to metabolic imaging, we used hyperpolarized pyruvate for perfusion-weighted imaging. This was consistent with conventional imaging for assessment of infarct size and blood flow. Lastly, we confirmed the translatability of simultaneous assessment of metabolism and perfusion with hyperpolarized MRI in healthy volunteers. In conclusion, hyperpolarized [1-13C]pyruvate may aid penumbral characterization and increase access to reperfusion therapy for late presenting patients.

Purpose: To investigate the potential effects of [1‐13C]lactate RF saturation pulses on [13C]bicarbonate detection in hyperpolarized [1‐13C]pyruvate MRI of the brain. Methods: Thirteen healthy rats underwent MRI with hyperpolarized [1‐13C]pyruvate of either the brain (n = 8) or the kidneys, heart, and liver (n = 5). Dynamic, metabolite‐selective imaging was used in a cross‐over experiment in which [1‐13C]lactate was excited with either 0° or 90° flip angles. The [13C]bicarbonate SNR and apparent [1‐13C]pyruvate‐to‐[13C]bicarbonate conversion (kPB) were determined. Furthermore, simulations were performed to identify the SNR optimal flip‐angle scheme for detection of [1‐13C]lactate and [13C]bicarbonate. Results: In the brain, the [13C]bicarbonate SNR was 64% higher when [1‐13C]lactate was not excited (5.8 ± 1.5 vs 3.6 ± 1.3; 1.2 to 3.3–point increase; p = 0.0027). The apparent kPB decreased 25% with [1‐13C]lactate saturation (0.0047 ± 0.0008 s−1 vs 0.0034 ± 0.0006 s−1; 95% confidence interval, 0.0006–0.0019 s−1 increase; p = 0.0049). These effects were not present in the kidneys, heart, or liver. Simulations suggest that the optimal [13C]bicarbonate SNR with a TR of 1 s in the brain is obtained with [13C]bicarbonate, [1‐13C]lactate, and [1‐13C]pyruvate flip angles of 60°, 15°, and 10°, respectively. Conclusions: Radiofrequency saturation pulses on [1‐13C]lactate limit [13C]bicarbonate detection in the brain specifically, which could be due to shuttling of lactate from astrocytes to neurons. Our results have important implications for experimental design in studies in which [13C]bicarbonate detection is warranted. [ABSTRACT FROM AUTHOR]

The cause of amyotrophic lateral sclerosis (ALS) is still unknown, and consequently, early diagnosis of the disease can be difficult and effective treatment is lacking. The pathology of ALS seems to involve specific disturbances in carbohydrate metabolism, which may be diagnostic and therapeutic targets. Magnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate is emerging as a technology for the evaluation of pathway-specific changes in the brain's metabolism. By imaging pyruvate and the lactate and bicarbonate it is metabolized into, the technology is sensitive to the metabolic changes of inflammation and mitochondrial dysfunction. In this study, we performed hyperpolarized MRI of a patient with newly diagnosed ALS. We found a lateralized difference in [1-13C]pyruvate-to-[1-13C]lactate exchange with no changes in exchange from [1-13C]pyruvate to 13C-bicarbonate. The 40% increase in [1-13C]pyruvate-to-[1-13C]lactate exchange corresponded with the patient's symptoms and presentation with upper-motor neuron affection and cortical hyperexcitability. The data presented here demonstrate the feasibility of performing hyperpolarized MRI in ALS. They indicate potential in pathway-specific imaging of dysfunctional carbohydrate metabolism in ALS, an enigmatic neurodegenerative disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke patients benefit from reperfusion in a short time-window after debut. Later treatment may be indicated if viable brain tissue is demonstrated and this outweighs the inherent risks of late reperfusion. Magnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate is an emerging technology that directly images metabolism. Here, we investigated its potential to detect viable tissue in ischemic stroke. Stroke was induced in pigs by intracerebral injection of endothelin 1. During ischemia, the rate constant of pyruvate-to-lactate conversion, k PL, was 52% larger in penumbra and 85% larger in the infarct compared to the contralateral hemisphere (P = 0.0001). Within the penumbra, the k PL was 50% higher in the regions that later infarcted compared to non-progressing regions (P = 0.026). After reperfusion, measures of pyruvate-to-lactate conversion were slightly decreased in the infarct compared to contralateral. In addition to metabolic imaging, we used hyperpolarized pyruvate for perfusion-weighted imaging. This was consistent with conventional imaging for assessment of infarct size and blood flow. Lastly, we confirmed the translatability of simultaneous assessment of metabolism and perfusion with hyperpolarized MRI in healthy volunteers. In conclusion, hyperpolarized [1-13C]pyruvate may aid penumbral characterization and increase access to reperfusion therapy for late presenting patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential effects of [1- 13 C]lactate RF saturation pulses on [ 13 C]bicarbonate detection in hyperpolarized [1- 13 C]pyruvate MRI of the brain., Methods: Thirteen healthy rats underwent MRI with hyperpolarized [1- 13 C]pyruvate of either the brain (n = 8) or the kidneys, heart, and liver (n = 5). Dynamic, metabolite-selective imaging was used in a cross-over experiment in which [1- 13 C]lactate was excited with either 0° or 90° flip angles. The [ 13 C]bicarbonate SNR and apparent [1- 13 C]pyruvate-to-[ 13 C]bicarbonate conversion (k PB ) were determined. Furthermore, simulations were performed to identify the SNR optimal flip-angle scheme for detection of [1- 13 C]lactate and [ 13 C]bicarbonate., Results: In the brain, the [ 13 C]bicarbonate SNR was 64% higher when [1- 13 C]lactate was not excited (5.8 ± 1.5 vs 3.6 ± 1.3; 1.2 to 3.3-point increase; p = 0.0027). The apparent k PB decreased 25% with [1- 13 C]lactate saturation (0.0047 ± 0.0008 s -1 vs 0.0034 ± 0.0006 s -1 ; 95% confidence interval, 0.0006-0.0019 s -1 increase; p = 0.0049). These effects were not present in the kidneys, heart, or liver. Simulations suggest that the optimal [ 13 C]bicarbonate SNR with a TR of 1 s in the brain is obtained with [ 13 C]bicarbonate, [1- 13 C]lactate, and [1- 13 C]pyruvate flip angles of 60°, 15°, and 10°, respectively., Conclusions: Radiofrequency saturation pulses on [1- 13 C]lactate limit [ 13 C]bicarbonate detection in the brain specifically, which could be due to shuttling of lactate from astrocytes to neurons. Our results have important implications for experimental design in studies in which [ 13 C]bicarbonate detection is warranted., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Magnetic resonance imaging (MRI) with hyperpolarized [1- 13 C]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- 13 C]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 13 C-pyruvate to 13 C-lactate conversion were calculated, including the k PL , 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 k PL across all examinations in the multisite comparison was 0.024 ± 0.0016 s -1 . The ICC of the k PL 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- 13 C]pyruvate to lactate using model-based metrics such as k PL suggests close agreement between sites and examinations in volunteers. Our initial results support harmonization of protocols, support multicenter studies, and inform their design.