Introduction

Proton MR spectroscopy has proven to be a valuable tool in the evaluation and detection of prostate cancer by assessing metabolite ratios incorporating choline and citrate signals. The intensity of the choline peak has been shown to increase in prostate cancer lesions, whereas the citrate peak decreases [1]. The choline peak in the proton spectrum actually consists of several different peaks of choline containing compounds[2], of which some can be distinguished using 7 Tesla ³¹P spectroscopic imaging [3,4]. By performing ³¹P and ¹H MRSI within one measurement, the total choline ¹H resonance can be correlated to the ³¹P peaks of the different choline containing compounds. This provides additional information about prostate cancer biology and may give an additional parameter in assessing prostate cancer aggressiveness. In this abstract we present a method for combining ³¹P and ¹H MRSI and show our first in vivo results.

Methods

Measurements were performed on a 7T whole-body MR system (MAGNETOM, Siemens Healthineers, Erlangen, Germany). An 8 channel multi-transmit body array coil was used in combination with an endorectal coil that featured a separate receive channel for ¹H and a Tx/Rx channel for ³¹P (Figure 1). After local B₀ and B₁ shimming [5], a multiparametric MRI protocol (transversal T2W and diffusion weighted imaging) [6] was performed in combination with proton and phosphorus MRSI. Proton MRSI was performed using a PRESS-like sequence with RF pulses that are both spectrally and spatially selective (Figure 2) [7], such that a VOI is excited of only the spectral region of interest (2.3-3.3 ppm) (TR=1000ms, TE= 135 ms, 1 average, FOV=84x70x70mm3, 12x10x10 matrix, 50% Hamming filter, true voxel size=0.94cc and acquisition time=7:01 min). ³¹P MRSI was performed using a 3D phase-encoded pulse-acquire sequence with a non-selective BIR-4 excitation pulse (flip angle= 45⁰, TR=1500ms, FOV=120x100x100 mm3, 12x10x10 matrix, 100% Hamming filter, 4 weighted averages, true voxel size=4.2cc, acquisition time 13:09 min). 4 patients with histopathologically proven prostate cancer (Gleason 4+4, 3+4, 3+4 and one unknown Gleason score) were measured using this setup. The data for the phosphorus MRSI was fit using Metabolite Report (Siemens Healthineers Erlangen, Germany). ¹H spectra were qualitatively assessed.

Results

All prostate cancer lesions were clearly identified on T2W and ADC imaging and in 3 out of 4 patients (patient 2, 3 and 4) a well distinguishable choline peak was present in the ¹H spectra of the tumor (Figures 3 and 4). Lipids in some cases contaminated the ¹H citrate signal, but did not influence the choline signal. Spermine signals had high intensities, due to refocusing the J-coupling with the spectrally selective pulses [7]. The ³¹P-MRSI measurement showed phosphocreatine (PCr) (low intensity within prostate, large signals from surrounding muscles) and the well-separated phosphomonoesters phosphoethanolamine (PE) and phosphocholine (PC) in all patients,. The phosphodiesters glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) were occasionally detectable and if both present, they were also well-separated. In patient 4 the ³¹P metabolite maps had strong asymmetry: the GPC+GPE and PC+PE metabolite maps showed a high intensity specifically within the prostate cancer lesion, whereas the smooth muscle PCr signals outside the prostate appeared highest on the contralateral side. Assuming a symmetric muscle PCr muscle signal, this indicates distinctly increased levels of GPC+GPE and PC+PE within the cancer lesion (Figure 4). In this lesion a highly elevated ¹H choline signal was also present, whereas it was completely absent in the contralateral prostate side.

Discussion

The described method can be used to obtain ³¹P as well as ¹H spectroscopic data of the prostate within one measurement and can correlate ³¹P choline compounds to the ¹H choline signal. The use of an endorectal coil hinders absolute quantification, hence we need to rely on relative signal intensities, ratios, or asymmetries. Metabolite ratios such as choline/spermine can be used to this extent for ¹H MRSI. ³¹P Ratios of PE, PC, GPE and GPC can provide information about metabolic pathways and are therefore suitable candidates for ³¹P MRSI. yATP and PCr may also to some extend serve as reference values. A high choline/spermine ratio can then be linked to ³¹P metabolite ratios. Due to the small patient group at the moment, no clinical conclusions can be drawn from the data yet, but preliminary anecdotal results indicate that the increase in ¹H choline in some high Gleason score prostate cancer lesions might partly be caused by a specific increase in GPC+GPE, which agrees with the results that were found by Lagemaat et al [3].

Conclusion

³¹P and ¹H spectroscopy can be performed within one measurement and enables an in vivo correlation between ¹H and ³¹P metabolite ratios.

Acknowledgements

Dutch Cancer Society [2014-6624]

References

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