Purpose

Sodium (²³Na) and advanced ¹H imaging techniques provide valuable metabolic information but are not routinely used because of the required additional scan time. The idle times in ²³Na MRI could be used to perform ¹H measurements^1,2, reducing scan time.
An interleaved radial amine CEST and sodium (INTERLACED) pulse sequence is proposed to simultaneously acquire acidity or T₂* and salinity maps without applying hardware modifications. We present phantom and data acquired dynamically in the leg during an exercise paradigm.

Methods

Experiments were done at 3T (Prisma, Siemens) on 5 volunteers (28.4±6.2 y.o.) using a dual-tuned ¹H/²³Na birdcage coil (RAPID).
Saline solutions
Two phantom sets were prepared with varying pH, sodium and gadolinium concentrations as described in table 1.
Exercise paradigm
Straight-leg plantar flexions were performed inside the coil using an elastic rubber band. The first exercise lasted 5 minutes and subjects were instructed to reach a maximum level of fatigue. Eight minutes later a second exercise was performed where plantar flexions were performed until reaching intense levels of fatigue. The subject would then hold an isometric contraction for as long as possible. Dynamic MR measurements were performed during the initial 6 and 10 minutes of recovery for the first and second exercises, respectively, and during the isometric contraction.
Interleaved NMR
INTERLACED is described in figure 2. For each magnetization transfer ratio asymmetry (MTR_asym) map, 29 CEST off-resonance frequencies were sampled (-3.5 to -2.5, 3.5 to 2.5 and -0.3 to 0.3 ppm) in 0.1 ppm steps. For each saturation off-set, two acquisition trains were performed, each consisting of 5 CEST saturation pulses (Gaussian, 100-ms length each, 6 µT peak amplitude), 25 ¹H spokes and 6 ²³Na spokes. A multi-echo acquisition with no CEST pulses (INTERLACED-T₂*) was also used. Acquisition parameters are summarized in figure 2B.
Dynamic measurements alternated between INTERLACED (29 CEST off-sets), INTERLACED (S₀ reference, no CEST saturation) and INTERLACED-T₂*. During the isometric contraction, S₀ and the -0.3 to 0.3 ppm CEST off-sets were acquired only once, improving temporal resolution of subsequent MTR_asym maps from 53 to 33 seconds.
Data Analysis
Interleaved NMR
For each dataset_, ¹H images were reconstructed^3,4 individually while the ²³Na spokes were reconstructed as a single image. T₂* values were calculated using an exponential decay of the multi-echo data.
CEST
Following the B₀ correction via a z-spectra based k-means clustering and Lorentzian fitting⁵, 0.4 ppm-width integrals S were estimated and MTR_asym calculated as MTR_asym(ω)=S(−ω)/S₀−S(ω)/S₀, with ω=3.0 ppm.
Statistical analysis
Similarity between interleaved and mononuclear measurements in phantoms was evaluated with intraclass correlation coefficients (ICC). In the exercise paradigm, relative changes to resting values were estimated using Wilcoxon rank sum tests.

Results and Discussion

INTERLACED and INTERLACED-T₂* reduced the acquisition time by 45.8% and 42.9%, respectively, relative to sequential mononuclear sequences.
Phantom results are shown in figure 3. The lowest ICC was found for MTR_asym(0.973), indicating an excellent correspondence between the interleaved and mononuclear measurements.
Figure 4 shows representative data from 2 subjects at different phases of the paradigm. Figure 5 shows the time courses for ²³Na signal, T₂* and MTR_asym relative to pre-exercise values. All subjects maintained the isometric contractions for least 256 seconds and stopped within the next 30 seconds. Similarly to previous studies⁶, during the first exercise trends of increased T₂* values in gastrocnemius muscles (Gas) with concomitant decreases in the soleus (Sol) were observed. A trend of increased T₂* in the tibialis anterior (TA) and a mild initial increase of the ²³Na signal in Gas were also observed. During the isometric contraction following the second exercise, strong T₂* decreases were observed, particularly in some volunteers in Gas (figure 4), likely caused by hemoglobin desaturation. The elevated MTR_asym in this period indicates acidification of the extracellular space, as amine CEST is insensitive to intracellular pH due to its elevated phosphate concentration⁷. Elevated MTR_asym might be observed only during the tetanic contraction but not during muscle recovery due to a potential reduction in blood flow, allowing ions to accumulate. Additional blood flow measurements are needed to validate this hypothesis. Sodium signal intensity also remained elevated during the isometric contraction and progressively decreased during recovery, as observed elsewhere following an intense exercise^8,9. The increase of sodium in Sol and Gas but not TA, could reflect an intracellular sodium concentration increase from transient Na⁺-K⁺ pump inactivation.

Conclusion

INTERLACED reduced the total scan time and allowed acquiring dynamic multinuclear data during an exercise paradigm. The sequence can be adapted to acquire other 1H contrasts, such as T2*. This approach will potentially contribute to the inclusion of sodium and advanced 1H MRI into clinical studies.

Acknowledgements

No acknowledgement found.

References

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