Introduction

The natural abundance ¹⁷O MR signal in vivo ranks third after proton and sodium. For the same acquisition interval, the ¹⁷O signal is 3 times less than sodium ¹. Thus, the capability of the ¹⁷O MRI for in vivo studies at the magnetic field of 21.1 T (NHMFL, Tallahassee) is a promising tool. It is already expected that the increased magnetic field can bring a gain in scan time or in imaging resolution. However, the ultra-high magnetic field can also change ¹⁷O MR relaxation times, which will be demonstrated below. The main goal of this study is to explore the capability of ¹⁷O in vivo MRI at 21.1 T and present the results of using labeled ¹⁷O glucose and ¹⁷O water as the first steps for future tumor detection based on the Warburg effect.

Methods

The MR experiments were performed on a 21.1 T magnet using Bruker MRI Avance III console (PV 5.1). The MR frequency for ¹⁷O was 121.65 MHz. The in vivo RF probe has a double tuned ¹⁷O/¹H volume RF coil with an internal diameter of 33 mm, covering the whole rat head. Duration of the 90 RF pulse for ¹⁷O in vivo was 165 μs. The ¹⁷O MR relaxation times T₁ and T₂ were measured using 180°-t-90° or 90°-t-180° pulse sequences respectively using 256 steps, NA = 16. Both data were fitted by a single exponential function. 3D MR rat head imaging scans were performed using a modified Bruker UTE pulse sequence with voxel of 1 mL, matrix 64x64x64, FOV=64x64x64 mm, TR = 15 ms, TE = 0.2 ms, NA = 16 for natural ¹⁷O abundance or NA=1 after ¹⁷O enrichments. Scan time in the last case was 1.5 min. The time course of ¹⁷O MR signal was investigated after IV tail injections of 1 mL PBS solution containing 17% enriched H₂¹⁷O or 1.5 ml of PBS with 500 mg of 6-¹⁷O 47% enriched D-glucose. The in vivo experiments were performed using 3 male Fisher 344 rats (~ 200 g). All animal experiments were conducted according to the protocols approved by The Florida State University ACUC.

Results and Discussion

The relaxation times T₁ and T₂ at 21.1 T are presented in comparison to the previous data of others at a lower magnetic field ^{2, 3} (Fig. 1). It was found that T₂ of ¹⁷O in a rat head was 2.07 ± 0.03 ms (n = 3), which is much less than the 3.03 ms found earlier at 9.4 T ². The corresponding T₁ relaxation time at 21.1 T was 5.35 ± 0.09 ms (n=3), which is a bit higher than at 9.4 T and close to 16.4 T ³. Additionally, the ¹⁷O MR relaxation times in 0.45% saline solution, are both larger at 21.1 T (T₁ = 7.6 ± 0.24 ms, T₂ = 6.5 ± 0.2 ms) than at 9.4 T (T₁= 6.5 ms, T₂=4.1 ms) ². Thus, the ¹⁷O MR relaxation mechanism is dependent on the strength of the magnetic field, as was also observed for sodium ^{4, 5}. 3D MRI of ¹⁷O in a rat head can be acquired with a resolution of 1x1x1 mm with a scan time of 1.5 min after an IV injection of 1 ml of 17% enriched H₂¹⁷O (Fig. 2). The image acquired one minute after ¹⁷O water injection demonstrated the increased perfusion of the rat brain and cortical areas. The ¹⁷O water signal decreased after the injection due to its distribution inside the rat body with the exponential decay time of 11 ± 0.4min (n=2). Injection of the 6-¹⁷O labeled glucose yielded in 1.5 minutes a separate MR peak of glucose well separated from the ¹⁷O water signal (Fig. 3). The glucose peak, after the initial bolus passage, was slowly decreasing as a result of glucose metabolism (Fig 3). The exponential glucose breakdown time was 48.2 ± 1.9 min (n=2). At the same time the rate of increase for the ¹⁷O MR water peak was ~ 1.5 times less.

Conclusion

The results demonstrate that ¹⁷O MR relaxation times are dependent on the strength of the magnetic field which correlates with the earlier observations for sodium. The well separated ¹⁷O MR signals of glucose and water at the ultra-high magnetic field and the corresponding time courses provided separate rates of water distribution and glucose consumption in the rat head. 3D ¹⁷O MRI is possible with a resolution of 1 mm³ in the rat head. Thus, enriched oxygen MRI can be a promising tool for future tumor detection based on the Warburg hypothesis and for evaluating the rates of glucose metabolism in tumors.

Acknowledgements

The study was performed at the National High Magnetic Field Laboratory (Tallahassee) supported by NSF, grant No. DMR-115490. Many thanks to Richard Desilets, Ashley Blue, Jason Kitchen, Malathy Elumalai, and Peter Gor’kov for their valuable help with RF probes.

References

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