Evidence of 13 C-lactate oxidation in the human brain from hyperpolarized 13 C-MRI.

PURPOSE: To test the hypothesis that lactate oxidation contributes to the 13 $$ {}^{13} $$ C-bicarbonate signal observed in the awake human brain using hyperpolarized 13 $$ {}^{13} $$ C MRI. METHODS: Healthy human volunteers (N = 6) were scanned twice using hyperpolarized 13 $$ {}^{13} $$ C-MRI, with increased radiofrequency saturation of 13 $$ {}^{13} $$ C-lactate on one set of scans. 13 $$ {}^{13} $$ C-lactate, 13 $$ {}^{13} $$ C-bicarbonate, and 13 $$ {}^{13} $$ C-pyruvate signals for 132 brain regions across each set of scans were compared using a clustered Wilcoxon signed-rank test. RESULTS: Increased 13 $$ {}^{13} $$ C-lactate radiofrequency saturation resulted in a significantly lower 13 $$ {}^{13} $$ C-bicarbonate signal (p = 0.04). These changes were observed across the majority of brain regions. CONCLUSION: Radiofrequency saturation of 13 $$ {}^{13} $$ C-lactate leads to a decrease in 13 $$ {}^{13} $$ C-bicarbonate signal, demonstrating that the 13 $$ {}^{13} $$ C-lactate generated from the injected 13 $$ {}^{13} $$ C-pyruvate is being converted back to 13 $$ {}^{13} $$ C-pyruvate and oxidized throughout the human brain.

Age-associated change in pyruvate metabolism investigated with hyperpolarized 13 C-MRI of the human brain.

In this study, hyperpolarized 13 C MRI (HP-13 C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized 13 C-pyruvate was administered to healthy aging individuals (N = 35, ages 21-77) and whole-brain spatial distributions of 13 C-lactate and 13 C-bicarbonate production were measured. Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized 13 C-lactate and normalized 13 C-bicarbonate production with age: - 7 % ± 2 % per decade for 13 C-lactate and - 9 % ± 4 % per decade for 13 C-bicarbonate. Certain regions, such as the right medial precentral gyrus, showed greater rates of change while the left caudate nucleus had a flat 13 C-lactate versus age and a slightly increasing 13 C-bicarbonate versus age. The results show that both the production of lactate (visible as 13 C-lactate signal) as well as the consumption of monocarboxylates to make acetyl-CoA (visible as 13 C-bicarbonate signal) decrease with age and that the rate of change varies by brain region.

Predicting response to radiotherapy of intracranial metastases with hyperpolarized [Formula: see text]C MRI.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. METHODS: Patients with intracranial metastases (N = 11) were scanned using hyperpolarized [Formula: see text]C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). RESULTS: The positive predictive value of [Formula: see text]C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 [Formula: see text], and the AUC from an ROC analysis was 0.77 [Formula: see text]. The distribution of [Formula: see text]C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, [Formula: see text]). CONCLUSIONS: Hyperpolarized [Formula: see text]C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.

Lactate topography of the human brain using hyperpolarized 13C-MRI.

Lactate is now recognized as an important intermediate in brain metabolism, but its role is still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected 13C-pyruvate over the whole brain using a new imaging method, hyperpolarized 13C MRI (N = 14, ages 23 to 77). Segmenting the 13C-lactate images into brain atlas regions revealed a pattern of lactate that was preserved across individuals. Higher lactate signal was observed in cortical grey matter compared to white matter and was highest in the precuneus, cuneus and lingual gyrus. Bicarbonate signal, indicating flux of [1-13C]pyruvate into the TCA cycle, also displayed consistent spatial distribution. One-way ANOVA to test for significant differences in lactate among atlas regions gave F = 87.6 and p < 10-6. This report of a "lactate topography" in the human brain and its consistent pattern is evidence of region-specific lactate biology that is preserved across individuals.

Partial Fourier reconstruction for improved resolution in 3D hyperpolarized 13 C EPI.

PURPOSE: Asymmetric in-plane k-space sampling of EPI can reduce the minimum achievable TE in hyperpolarized 13C with spectral-spatial radio frequency pulses, thereby reducing T2* weighting and signal-losses. Partial Fourier image reconstruction exploits the approximate Hermitian symmetry of k-space data and can be applied to asymmetric data sets to synthesize unmeasured data. Here we tested whether the application of partial Fourier image reconstruction would improve spatial resolution from hyperpolarized [1- 13C ]pyruvate scans in the human brain. METHODS: Fifteen healthy control subjects were imaged using a volumetric dual-echo echo-planar imaging sequence with spectral-spatial radio frequency excitation. Images were reconstructed by zero-filling as well as with the partial Fourier reconstruction algorithm projection-on-convex-sets. Resulting images were quantitatively evaluated with a no-reference image quality assessment. RESULTS: The no-reference image sharpness metric agreed with perceived improvements in image resolution and contrast. The [1- 13C ]lactate images benefitted most, followed by the [1- 13C ]pyruvate images. The 13C -bicarbonate images were improved by the smallest degree, likely owing to relatively lower SNR. CONCLUSIONS: Partial Fourier imaging and reconstruction were shown to improve the sharpness and contrast of human HP 13C brain data and is a viable method for enhancing resolution.

Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience.

RATIONALE: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. OBJECTIVE: To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart. METHODS AND RESULTS: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1-13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1-13C]lactate. CONCLUSIONS: These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1-13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.

Task Activation Results in Regional 13 C-Lactate Signal Increase in the Human Brain.

Hyperpolarized- 13 C magnetic resonance imaging (HP- 13 C MRI) was used to image changes in 13 C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain 13 C-pyruvate, 13 C-lactate and 13 C-bicarbonate production was imaged in healthy volunteers (N=6, ages 24-33) for the two conditions using two separate hyperpolarized 13 C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation. 13 C-metabolite signal was normalized by 13 C-metabolite signal from the brainstem and the percentage change in 13 C-metabolite signal conditions was calculated. A one-way Wilcoxon signed-rank test showed a significant increase in 13 C-lactate in regions of activation when compared to the remainder of the brain ( p = 0.02, V = 21). No significant increase was observed in 13 C-pyruvate ( p = 0.11, V = 17) or 13 C-bicarbonate ( p = 0.95, V = 3) signal. The results show an increase in 13 C-lactate production in the activated region that is measurable with HP- 13 C MRI.