Optimal treatment selection for localized renal tumors is challenging due to their variable biological behavior and limited ability to pre-operatively assess their aggressiveness. We investigated hyperpolarized (HP) ¹³C pyruvate MRI to noninvasively assess tumor lactate production and compartmentalization, which are strongly associated with renal tumor aggressiveness. Orthotopic tumors were created in mice using human renal cell carcinoma (RCC) lines (A498, 786-O, UOK262) with varying expression of lactate dehydrogenase A (LDHA) which catalyzes the pyruvate-to-lactate conversion, and varying expression of monocarboxylate transporter 4 (MCT4) which mediates lactate export out of the cells. Dynamic HP ¹³C pyruvate MRI showed that the A498 tumors had significantly higher ¹³C pyruvate-to-lactate conversion than the UOK262 and 786-O tumors, corresponding to higher A498 tumor LDHA expression. Additionally, diffusion-weighted HP ¹³C pyruvate MRI showed that the A498 tumors had significantly higher ¹³C lactate apparent diffusion coefficients compared to 786-O tumors, with corresponding higher MCT4 expression, which likely reflects more rapid lactate export in the A498 tumors. Our data demonstrate the feasibility of HP ¹³C pyruvate MRI to inform on tumor lactate production and compartmentalization, and provide the scientific premise for future clinical investigation into the utility of this technique to noninvasively interrogate renal tumor aggressiveness and to guide treatment selection.

The cerebral metabolic rate of oxygen consumption (CMRO₂) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO₂ can be measured by direct ¹⁷O magnetic resonance imaging (¹⁷O-MRI) of H₂¹⁷O signal changes during inhalation of ¹⁷O-labeled oxygen gas. In this study, we built a simple gas distribution system and used 3D zero echo time (ZTE-)MRI at 11.7 T to measure CMRO₂ in the APP_swe/PS1_dE9 mouse model of amyloidosis. We found that CMRO₂ was significantly lower in the APP_swe/PS1_dE9 brain than in wild-type at 12–14 months. We also estimated cerebral blood flow (CBF) from the post-inhalation washout curve and found no difference between groups. These results suggest that the lower CMRO₂ observed in APP_swe/PS1_dE9 is likely due to metabolism impairment rather than to reduced blood flow. Analysis of the ¹⁷O-MRI data using different quantification models (linear and 3-phase model) showed that the choice of the model does not affect group comparison results. However, the simplified linear model significantly underestimated the absolute CMRO₂ values compared to a 3-phase model. This may become of importance when combining several metabolic fluxes measurements to study neuro-metabolic coupling.

Microvascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured noninvasively and quantitatively by arterial spin labeling (ASL) MRI. Most studies using ASL in muscle have only reported data from a single slice, thereby assuming that muscle perfusion is homogeneous within muscle, whereas recent literature has reported proximodistal differences in oxidative capacity and perfusion. Here, we acquired pulsed ASL data in 12 healthy volunteers after dorsiflexion exercise in two slices separated distally by 7 cm. We combined this with a Look‐Locker scheme to acquire images at multiple postlabeling delays (PLDs) and with a multiecho readout to measure T₂*. This enabled the simultaneous evaluation of quantitative muscle blood flow (MBF), arterial transit time (ATT), and T₂* relaxation time in the tibialis anterior muscle during recovery. Using repeated measures analyses of variance we tested the effect of time, slice location, and their interaction on MBF, ATT, and T₂*. Our results showed a significant difference as a function of time postexercise for all three parameters (MBF: F = 34.0, p < .0001; T₂*: F = 73.7, p < .0001; ATT: F = 13.6, p < .001) and no average differences between slices over the total time postexercise were observed. The interaction effect between time postexercise and slice location was significant for MBF and T₂* (F = 5.5, p = 0.02, F = 6.1, p = 0.02, respectively), but not for ATT (F = 2.2, p = .16). The proximal slice showed a higher MBF and a lower ATT than the distal slice during the first 2 min of recovery, and T₂* showed a delayed response in the distal slice. These results imply a higher perfusion and faster microvascular response to exercise in the proximal slice, in line with previous literature. Moreover, the differences in ATT indicate that it is difficult to correctly determine perfusion based on a single PLD as is commonly performed in the muscle literature.

Purpose: Multislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low‐perfusion SNR in distal slices when large spatial coverage is required. However, fiber type and oxidative capacity vary along the length of healthy muscles, calling for multislice acquisitions in clinical studies. We propose a new variant of flow alternating inversion recovery (FAIR) that generates sufficient ASL signal to monitor exercise‐induced perfusion changes in muscle in two distant slices.Methods: Label around and between two 7‐cm distant slices was created by applying the presaturation/postsaturation and selective inversion modules selectively to each slice (split‐label multislice FAIR). Images were acquired using simultaneous multislice EPI. We validated our approach in the brain to take advantage of the high resting‐state perfusion, and applied it in the lower leg muscle during and after exercise, interleaved with a single‐slice FAIR as a reference.Results: We show that standard multislice FAIR leads to an underestimation of perfusion, while the proposed split‐label multislice approach shows good agreement with separate single‐slice FAIR acquisitions in brain, as well as in muscle following exercise.Conclusion: Split‐label FAIR allows measuring muscle perfusion in two distant slices simultaneously without losing sensitivity in the distal slice.

Assessing CMRO ₂ during neuronal activation is essential to understanding brain energy metabolism and neurovascular coupling. Over the past decades, preclinical studies have yielded variable results, likely due to differences in techniques, models, and stimulation paradigms. Here, we present the first study using ¹⁷ O-MRI to directly quantify CMRO ₂ during paw electrical stimulation in rats at 11.7 T. CMRO ₂ was significantly higher in the activated cortex (3.28 ± 0.27 µmol/g/min) than in the control cortex (2.89 ± 0.32 µmol/g/min), corresponding to a 13.8% ± 7.9% increase. A strong negative correlation was found between ΔCMRO ₂ and resting CMRO ₂ , suggesting that baseline oxidative metabolism influences the evoked response. Flow-related parameters ( K _G , K _L , k _W ) and cerebral blood flow (CBF) were also estimated, revealing a significant 22% increase in CBF in the activated cortex. These findings demonstrate that ¹⁷ O-MRI is a robust, noninvasive tool for direct CMRO ₂ quantification during functional activation, with strong potential as a new standard for studying oxidative brain metabolism.