Search

Background Pyruvate dehydrogenase (PDH) and lactate dehydrogenase are essential for adenosine triphosphate production in skeletal muscle. At the onset of exercise, oxidation of glucose and glycogen is quickly enabled by dephosphorylation of PDH. However, direct measurement of PDH flux in exercising human muscle is daunting, and the net effect of covalent modification and other control mechanisms on PDH flux has not been assessed. Purpose To demonstrate the feasibility of assessing PDH activation and changes in pyruvate metabolism in human skeletal muscle after the onset of exercise using carbon 13 (13C) MRI with hyperpolarized (HP) [1-13C]-pyruvate. Materials and Methods For this prospective study, sedentary adults in good general health (mean age, 42 years ± 18 [standard deviation]; six men) were recruited from August 2019 to September 2020. Subgroups of the participants were injected with HP [1-13C]-pyruvate at resting, during plantar flexion exercise, or 5 minutes after exercise during recovery. In parallel, hydrogen 1 arterial spin labeling MRI was performed to estimate muscle tissue perfusion. An unpaired t test was used for comparing 13C data among the states. Results At rest, HP [1-13C]-lactate and [1-13C]-alanine were detected in calf muscle, but [13C]-bicarbonate was negligible. During moderate flexion-extension exercise, total HP 13C signals (tC) increased 2.8-fold because of increased muscle perfusion (P = .005), and HP [1-13C]-lactate-to-tC ratio increased 1.7-fold (P = .04). HP [13C]-bicarbonate-to-tC ratio increased 8.4-fold (P = .002) and returned to the resting level 5 minutes after exercise, whereas the lactate-to-tC ratio continued to increase to 2.3-fold as compared with resting (P = .008). Conclusion Lactate and bicarbonate production from hyperpolarized (HP) [1-carbon 13 {13C}]-pyruvate in skeletal muscle rapidly reflected the onset and the termination of exercise. These results demonstrate the feasibility of imaging skeletal muscle metabolism using HP [1-13C]-pyruvate MRI and the sensitivity of in vivo pyruvate metabolism to exercise states. © RSNA, 2021 Online supplemental material is available for this article.

77Se is a spin 1/2 ${{ 1/2 }}$ , low sensitivity nucleus with a natural abundance of 7.6 %. Although 77Se NMR is very useful in the characterization of selenium containing molecules including seleno‐proteins, the detection of 77Se is challenging in biological samples without enrichment. Therefore, the goal of this work was to establish whether the 77Se signal could be enhanced in the liquid state by dissolution dynamic nuclear polarization (DNP) NMR without the need of enrichment. The dominant spin‐lattice relaxation mechanism for 77Se is via chemical shift anisotropy, which is highly dependent on the molecular symmetry. Here we tested three selenium compounds (sodium selenate, sodium selenite and selenocystine) with different molecular symmetries in dissolution DNP experiments and demonstrated that 77Se DNP using commercially available hardware is feasible but the achieved NMR signal enhancements (1368‐fold for selenate, 125‐fold for selenite and no enhancement for selenocystine at 9.4 T) were strongly dependent on molecular symmetry. [ABSTRACT FROM AUTHOR]

Purpose: This study is to investigate time‐resolved 13C MR spectroscopy (MRS) as an alternative to imaging for assessing pyruvate metabolism using hyperpolarized (HP) [1‐13C]pyruvate in the human brain. Methods: Time‐resolved 13C spectra were acquired from four axial brain slices of healthy human participants (n = 4) after a bolus injection of HP [1‐13C]pyruvate. 13C MRS with low flip‐angle excitations and a multichannel 13C/1H dual‐frequency radiofrequency (RF) coil were exploited for reliable and unperturbed assessment of HP pyruvate metabolism. Slice‐wise areas under the curve (AUCs) of 13C‐metabolites were measured and kinetic analysis was performed to estimate the production rates of lactate and HCO3‐. Linear regression analysis between brain volumes and HP signals was performed. Region‐focused pyruvate metabolism was estimated using coil‐wise 13C reconstruction. Reproducibility of HP pyruvate exams was presented by performing two consecutive injections with a 45‐minutes interval. Results: [1‐13C]Lactate relative to the total 13C signal (tC) was 0.21–0.24 in all slices. [13C]HCO3‐/tC was 0.065–0.091. Apparent conversion rate constants from pyruvate to lactate and HCO3‐ were calculated as 0.014–0.018 s−1 and 0.0043–0.0056 s−1, respectively. Pyruvate/tC and lactate/tC were in moderate linear relationships with fractional gray matter volume within each slice. White matter presented poor linear regression fit with HP signals, and moderate correlations of the fractional cerebrospinal fluid volume with pyruvate/tC and lactate/tC were measured. Measured HP signals were comparable between two consecutive exams with HP [1‐13C]pyruvate. Conclusions: Dynamic MRS in combination with multichannel RF coils is an affordable and reliable alternative to imaging methods in investigating cerebral metabolism using HP [1‐13C]pyruvate. [ABSTRACT FROM AUTHOR]

Purpose: Previous cardiac imaging studies using hyperpolarized (HP) [1‐13C]pyruvate were acquired at end‐diastole (ED). Little is known about the interaction between cardiac cycle and metabolite content in the myocardium. In this study, we compared images of HP pyruvate and products at end‐systole (ES) and ED. Methods: A dual‐phase 13C MRI sequence was implemented to acquire two sequential HP images within a single cardiac cycle at ES and ED during successive R‐R intervals in an interleaved manner. Each healthy volunteer (N = 3) received two injections of HP [1‐13C]pyruvate for the dual‐phase imaging on the short‐axis and the vertical long‐axis planes. Spatial distribution of HP 13C metabolites at each cardiac phase was correlated to multiphase 1H MRI to confirm the mechanical changes. Ratios of myocardial HP metabolites were compared between ES and ED. Segmental analysis was performed on the midcavity short‐axis plane. Results: In addition to mechanical changes, metabolic profiles of the heart detected by HP [1‐13C]pyruvate differed between ES and ED. The myocardial signal of [13C]bicarbonate relative to [1‐13C]lactate was significantly smaller at ED than the ratio at ES (p <.05), particularly in mid‐anterior and mid‐inferoseptal segments. The distinct metabolic profiles in the myocardium likely reflect the technical aspects of the imaging approach such as the coronary flow in addition to the cyclical changes in metabolism. Conclusion: The study demonstrates that metabolic profiles of the heart, measured by HP [1‐13C]pyruvate, are affected by the cardiac cycle in which that the data are acquired. [ABSTRACT FROM AUTHOR]

Purpose: Noninvasive imaging with hyperpolarized (HP) pyruvate can capture in vivo cardiac metabolism. For proper quantification of the metabolites and optimization of imaging parameters, understanding MR characteristics such as T2∗s of the HP signals is critical. This study is to measure in vivo cardiac T2∗s of HP [1‐13C]pyruvate and the products in rodents and humans. Methods: A dynamic 13C multi‐echo spiral imaging sequence that acquires [13C]bicarbonate, [1‐13C]lactate, and [1‐13C]pyruvate images in an interleaved manner was implemented for a clinical 3 Tesla system. T2∗ of each metabolite was calculated from the multi‐echo images by fitting the signal decay of each region of interest mono‐exponentially. The performance of measuring T2∗ using the sequence was first validated using a 13C phantom and then with rodents following a bolus injection of HP [1‐13C]pyruvate. In humans, T2∗ of each metabolite was calculated for left ventricle, right ventricle, and myocardium. Results: Cardiac T2∗s of HP [1‐13C]pyruvate, [1‐13C]lactate, and [13C]bicarbonate in rodents were measured as 24.9 ± 5.0, 16.4 ± 4.7, and 16.9 ± 3.4 ms, respectively. In humans, T2∗ of [1‐13C]pyruvate was 108.7 ± 22.6 ms in left ventricle and 129.4 ± 8.9 ms in right ventricle. T2∗ of [1‐13C]lactate was 40.9 ± 8.3, 44.2 ± 5.5, and 43.7 ± 9.0 ms in left ventricle, right ventricle, and myocardium, respectively. T2∗ of [13C]bicarbonate in myocardium was 64.4 ± 2.5 ms. The measurements were reproducible and consistent over time after the pyruvate injection. Conclusion: The proposed metabolite‐selective multi‐echo spiral imaging sequence reliably measures in vivo cardiac T2∗s of HP [1‐13C]pyruvate and products. [ABSTRACT FROM AUTHOR]

Purpose: This study is to investigate time-resolved 13 C MR spectroscopy (MRS) as an alternative to imaging for assessing pyruvate metabolism using hyperpolarized (HP) [1- 13 C]pyruvate in the human brain., Methods: Time-resolved 13 C spectra were acquired from four axial brain slices of healthy human participants (n = 4) after a bolus injection of HP [1- 13 C]pyruvate. 13 C MRS with low flip-angle excitations and a multichannel 13 C/ 1 H dual-frequency radiofrequency (RF) coil were exploited for reliable and unperturbed assessment of HP pyruvate metabolism. Slice-wise areas under the curve (AUCs) of 13 C-metabolites were measured and kinetic analysis was performed to estimate the production rates of lactate and HCO 3 - . Linear regression analysis between brain volumes and HP signals was performed. Region-focused pyruvate metabolism was estimated using coil-wise 13 C reconstruction. Reproducibility of HP pyruvate exams was presented by performing two consecutive injections with a 45-minutes interval., Results: [1- 13 C]Lactate relative to the total 13 C signal (tC) was 0.21-0.24 in all slices. [ 13 C] HCO 3 - /tC was 0.065-0.091. Apparent conversion rate constants from pyruvate to lactate and HCO 3 - were calculated as 0.014-0.018 s -1 and 0.0043-0.0056 s -1 , respectively. Pyruvate/tC and lactate/tC were in moderate linear relationships with fractional gray matter volume within each slice. White matter presented poor linear regression fit with HP signals, and moderate correlations of the fractional cerebrospinal fluid volume with pyruvate/tC and lactate/tC were measured. Measured HP signals were comparable between two consecutive exams with HP [1- 13 C]pyruvate., Conclusions: Dynamic MRS in combination with multichannel RF coils is an affordable and reliable alternative to imaging methods in investigating cerebral metabolism using HP [1- 13 C]pyruvate., (© 2021 International Society for Magnetic Resonance in Medicine.)

Background Pyruvate dehydrogenase (PDH) and lactate dehydrogenase are essential for adenosine triphosphate production in skeletal muscle. At the onset of exercise, oxidation of glucose and glycogen is quickly enabled by dephosphorylation of PDH. However, direct measurement of PDH flux in exercising human muscle is daunting, and the net effect of covalent modification and other control mechanisms on PDH flux has not been assessed. Purpose To demonstrate the feasibility of assessing PDH activation and changes in pyruvate metabolism in human skeletal muscle after the onset of exercise using carbon 13 ( 13 C) MRI with hyperpolarized (HP) [1- 13 C]-pyruvate. Materials and Methods For this prospective study, sedentary adults in good general health (mean age, 42 years ± 18 [standard deviation]; six men) were recruited from August 2019 to September 2020. Subgroups of the participants were injected with HP [1- 13 C]-pyruvate at resting, during plantar flexion exercise, or 5 minutes after exercise during recovery. In parallel, hydrogen 1 arterial spin labeling MRI was performed to estimate muscle tissue perfusion. An unpaired t test was used for comparing 13 C data among the states. Results At rest, HP [1- 13 C]-lactate and [1- 13 C]-alanine were detected in calf muscle, but [ 13 C]-bicarbonate was negligible. During moderate flexion-extension exercise, total HP 13 C signals (tC) increased 2.8-fold because of increased muscle perfusion ( P = .005), and HP [1- 13 C]-lactate-to-tC ratio increased 1.7-fold ( P = .04). HP [ 13 C]-bicarbonate-to-tC ratio increased 8.4-fold ( P = .002) and returned to the resting level 5 minutes after exercise, whereas the lactate-to-tC ratio continued to increase to 2.3-fold as compared with resting ( P = .008). Conclusion Lactate and bicarbonate production from hyperpolarized (HP) [1-carbon 13 { 13 C}]-pyruvate in skeletal muscle rapidly reflected the onset and the termination of exercise. These results demonstrate the feasibility of imaging skeletal muscle metabolism using HP [1- 13 C]-pyruvate MRI and the sensitivity of in vivo pyruvate metabolism to exercise states. © RSNA, 2021 Online supplemental material is available for this article.

Purpose: Noninvasive imaging with hyperpolarized (HP) pyruvate can capture in vivo cardiac metabolism. For proper quantification of the metabolites and optimization of imaging parameters, understanding MR characteristics such as T 2 ∗ s of the HP signals is critical. This study is to measure in vivo cardiac T 2 ∗ s of HP [1- 13 C]pyruvate and the products in rodents and humans., Methods: A dynamic 13 C multi-echo spiral imaging sequence that acquires [ 13 C]bicarbonate, [1- 13 C]lactate, and [1- 13 C]pyruvate images in an interleaved manner was implemented for a clinical 3 Tesla system. T 2 ∗ of each metabolite was calculated from the multi-echo images by fitting the signal decay of each region of interest mono-exponentially. The performance of measuring T 2 ∗ using the sequence was first validated using a 13 C phantom and then with rodents following a bolus injection of HP [1- 13 C]pyruvate. In humans, T 2 ∗ of each metabolite was calculated for left ventricle, right ventricle, and myocardium., Results: Cardiac T 2 ∗ s of HP [1- 13 C]pyruvate, [1- 13 C]lactate, and [ 13 C]bicarbonate in rodents were measured as 24.9 ± 5.0, 16.4 ± 4.7, and 16.9 ± 3.4 ms, respectively. In humans, T 2 ∗ of [1- 13 C]pyruvate was 108.7 ± 22.6 ms in left ventricle and 129.4 ± 8.9 ms in right ventricle. T 2 ∗ of [1- 13 C]lactate was 40.9 ± 8.3, 44.2 ± 5.5, and 43.7 ± 9.0 ms in left ventricle, right ventricle, and myocardium, respectively. T 2 ∗ of [ 13 C]bicarbonate in myocardium was 64.4 ± 2.5 ms. The measurements were reproducible and consistent over time after the pyruvate injection., Conclusion: The proposed metabolite-selective multi-echo spiral imaging sequence reliably measures in vivo cardiac T 2 ∗ s of HP [1- 13 C]pyruvate and products., (© 2021 International Society for Magnetic Resonance in Medicine.)