Abstract 11 C-acetate is a positron emission tomography (PET) tracer of oxidative metabolism, whereas hyperpolarized 13 C-acetate can be used in magnetic resonance imaging (MRI) for investigating specific metabolic processes. The aims of this study were to examine if the kinetic formalism of 11 C-acetate PET in the kidneys is comparable to that of 13 C-acetate MRI, and to compare the dynamic metabolic information of hyperpolarized 13 C-acetate MRI with that obtained with 11 C-acetate PET. Rats were examined with dynamic hyperpolarized 13 C-acetate MRI or 11 C-acetate PET before and after intravenous injection of furosemide, a loop diuretic known to alter both the hemodynamics and oxygen consumption in the kidney. The metabolic clearance rates (MCR) were estimated and compared between the two modalities experimentally in vivo and in simulations. There was a clear dependency on the mean transit time and MCR for both 13 C-acetate and 11 C-acetate following furosemide administration, while no dependencies on the apparent renal perfusion were observed. This study demonstrated that hyperpolarized 13 C-acetate MRI is feasible for measurements of the intrarenal energetic demand via the MCR, and that the quantitative measures are correlated with those measured by 11 C-acetate PET, even though the temporal window is more than 30 times longer with 11 C-acetate.
Abstract Background Long-COVID is an umbrella term used to describe ongoing symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is one of the most common and can persist for months after the initial infection. Investigations including Computed Tomography (CT), and physiological measurements (lung function tests) are usually unremarkable. The mechanisms driving breathlessness remain unclear, and this may be hindering the development of effective treatments. Methods Eleven non-hospitalised Long-COVID (NHLC, 4 male), 12 post-hospitalised COVID-19 (PHC, 10 male) patients were recruited from a Post-COVID Assessment clinic, and thirteen healthy controls (6 female) were recruited to undergo Hyperpolarized Xenon Magnetic Resonance Imaging (Hp-XeMRI). NHLC and PHC participants underwent contemporaneous CT, Hp-XeMRI, lung function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Statistical analysis included group and pair-wise comparisons between patients and controls, and correlations between patient clinical and imaging data. Results NHLC and PHC patients were 287 ± 79 [range 190-437] and 149 ± 68 [range 68-269] days from infection, respectively. All NHLC patients had normal CT scans, and the PHC had normal or near normal CT scans (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively). There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04) but no differences in other measurements of lung function. There were significant differences in RBC:TP mean between volunteers (0.45 ± 0.07, range [0.33-0.55]) and PHC (0.31 ± 0.11, [range 0.16-0.37]) and NHLC (0.35 ± 0.09, [range 0.26-0.58]) patients, but not between NHLC and PHC (p = 0.26). Conclusion There are RBC:TP abnormalities in NHLC and PHC patients, with NHLC patients also demonstrating lower TLco than PHC patients despite their having normal CT scans. These abnormalities are present many months after the initial infection. Summary statement Hyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal. Key results There are significant differences in RBC:TP mean between healthy controls and PHC/NHLC patients (0.45 ± 0.07, range [0.33-0.55], 0.31 ± 0.11, [range 0.16-0.37], 0.35 ± 0.09, [range 0.26-0.58], respectively, p < 0.05 after correction for multiple comparisons) indicating a change in lung compartment volumes between groups. There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04), despite normal or near normal FEV (%) (100 ± 13% [range 72-123%] and 88 ± 21% [range 62-113%], p>0.05. There were significant differences in CT abnormalities between NHLC and PHC patients (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively) despite similarly impaired RBC:TP.
Hyperpolarized 13 C imaging allows real-time in vivo measurements of metabolite levels. Quantification of metabolite conversion between [1- 13 C]pyruvate and downstream metabolites [1- 13 C]alanine, [1- 13 C]lactate, and [ 13 C]bicarbonate can be achieved through kinetic modeling. Since pyruvate interacts dynamically and simultaneously with its downstream metabolites, the purpose of this work is the determination of parameter values through a multisite, dynamic model involving possible biochemical pathways present in MR spectroscopy. Kinetic modeling parameters were determined by fitting the multisite model to time-domain dynamic metabolite data. The results for different pyruvate doses were compared with those of different two-site models to evaluate the hypothesis that for identical data the uncertainty of a model and the signal-to-noise ratio determine the sensitivity in detecting small physiological differences in the target metabolism. In comparison to the two-site exchange models, the multisite model yielded metabolic conversion rates with smaller bias and smaller standard deviation, as demonstrated in simulations with different signal-to-noise ratio. Pyruvate dose effects observed previously were confirmed and quantified through metabolic conversion rate values. Parameter interdependency allowed an accurate quantification and can therefore be useful for monitoring metabolic activity in different tissues.
To assess the feasibility of hyperpolarized (HP) (129)Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs.The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gy irradiation to the right lung using a (60)Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (LPT) and relative blood volume (VRBC) from each of the right and left lungs of both cohorts. Following imaging, lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements.Statistically significant differences in LPT and VRBC were observed between the irradiated and non-irradiated cohorts. In particular, LPT of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, VRBC of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the MRI measurements for both the non-irradiated (r = 0.79, P < 0.01) and irradiated groups (r = 0.91, P < 0.01).Regional RILI can be detected two weeks post-irradiation using HP (129)Xe MRI and analysis of gas exchange curves. This approach correlates well with histology and can potentially be used clinically to assess radiation pneumonitis associated with early RILI to improve radiation therapy outcomes.
Parallel imaging can aid hyperpolarized 13 C MRI in extracting more information in the limited time window of the hyperpolarized signal. Using a dedicated, flexible 13 C receive coil design with coupling coefficients matched for both 13 C and 23 Na, sensitivity profiles for reconstruction can be acquired at the 23 Na frequency. We demonstrate this method in two hyperpolarized in vivo experiments involving pig kidneys and human brain using a two-times accelerated 3D blipped stack-of-spirals sequence with dual-resolution. The results show good SNR, coverage, and resolution. The method is promising for integrating and automating parallel imaging for hyperpolarized 13 C MRI.
3D density-weighted MRSI was used to regionally measure the 129 Xe chemical shift from xenon in the lung airspaces (G), lung tissue/plasma (TP) and pulmonary red blood cells (RBC) at three lung inflation states. The 129 Xe-RBC and 129 Xe-G chemical shifts were both found to increase with increasing lung inflation (increase in alveolar pO2) while the 129 Xe-TP shift was observed to be lung-inflation independent. The RBC chemical shift maps presented here may be used in patient populations to detect areas of low blood oxygenation in diseases presenting regional hypoxia in the lungs and other well-perfused organs such as the brain and kidneys.
Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C–hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.
Sodium ( 23 Na)-MRI was performed using a dual-tuned bilateral 23 Na/ 1 H breast coil on seven patients with ductal carcinoma, one patient with lobular carcinoma, and ten normal volunteers. Several patients had [ 23 Na] measurements that were 2-3 times higher than the mean normal fibroglandular [ 23 Na] measurements. There were no strong correlations between 23 Na-MRI and either DCE or DWI measurements in the patients. These measurements suggest that [ 23 Na] may provide an additional physiological imaging mechanism of breast cancer.
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