Comments on ultrahigh field 31P ATP T2 values
A recent article by Lei et al. (1) described 31P spectral acquisitions in the human brain at 7 T. Measurements of the 31P metabolite relaxation times T1 and T2 were reported as were nuclear Overhauser enhancement (NOE) factors from 1H irradiation and rate constants for the creatine kinase reaction. Such studies are critical for understanding how experiments previously performed at lower field strengths will benefit from the use of ultrahigh field strength systems which are now appearing for human research and, ultimately, clinical use. On the whole, we agree with the authors that their results demonstrate considerable advantages for 31P studies of humans at such high field strengths. We have, however, some concerns regarding the T2 values for the α and γ 31P ATP resonances which the authors report and how they compare with existing literature values acquired at lower field strengths.
The T2 measurements from Lei et al. were made using a Hahn spin echo sequence with a 5-cm-diameter surface coil in transmit/receive mode to “cover the human primary visual cortex only (p. 199).” The Hahn spin echo sequence consisted of a hard 90° pulse of 0.2 ms duration followed by a band-selective refocusing pulse which “refocused the γ and α-ATP resonances, but not the β-ATP resonance (p. 200)” in order to “suppress the effect of 31P-31P J-modulation (p. 200).” With this arrangement, Lei et al. report α and γ 31P ATP T2 values of ∼26 ms at 7 T in the human brain.
Comparing their 7 T 31P metabolite relaxation times with those measured at other, lower, field strengths, Lei et al. make the general statement that “…no clear field dependence for T1 and T2 was identified (p. 203).” Justification for this statement appears in the literature synopsis contained in their table 2. Within that table, however, a curious discrepancy among previous ATP 31P T2 ATP measurements is observed. Namely, Remy et al. (2), at 4.7 T in rat brain, and Merboldt et al. (3), at 2 T in human brain, reported low T2 values in the 20–40 ms range. In contrast, Jung et al. (4) reported much longer 31P ATP T2 values in the 60–90 ms range for human brain at 1.5 T. In fact, Jung and colleagues (4-7) performed several studies in the 1990s of both skeletal muscle and brain in which the 31P ATP T2 values were measured to be much longer than those reported in the earlier studies (2, 3). They attributed the low T2 values reported in the early works (2, 3) to an incomplete accounting of J-coupling oscillations. The longer T2 values suggested by Jung and colleagues led us to attempt the use of multiecho sequences (8) to rapidly map ATP resonances in live mice at 4.7 T (9). Our moderate success in this endeavor was, we believe, due to in vivo 31P ATP T2 values in excess of 60 ms and properly taking into account AMX J-coupling oscillations among the three ATP resonances when considering echo spacings and performing image reconstructions (9).
Thus, we return to the 26 ms 31P ATP T2 values reported by Lei et al. (1) at 7 T in the human brain. Have the authors measured the actual T2 values or, as with the early reports, has J-coupling among the ATP phosphorous nuclei led to artificially low T2 values? The authors did employ a frequency-selective refocusing pulse in their Hahn spin echo acquisitions which, for perfect 90° and 180° flip angles, will eliminate J-coupling oscillations with TE for the α and γ resonances. Of course the use of a transmit/receive surface coil configuration for spatial localization makes perfect flip angle assumptions problematic. Phase cycling of the refocusing pulse and crusher gradients, both of which the authors state were employed, may have ameliorated this problem. However, the phase cycling scheme and any detailed description of how it “eliminates unwanted coherence transfer pathways (p. 200)” for an AMX system subjected to a Θαγ,β – TE/2 – (2Θ)α,γselective – TE/2 – acquire sequences as applied with a surface coil distribution of flip angles Θ were not provided in the article. Similarly, spectra at various echo times were not shown. Thus, it is difficult to assess the extent to which the reported T2 values for the 31P ATP resonances have or have not been affected by J-coupling. The authors may be confident that such problems have been overcome by their technique and that their 7 T 31P ATP T2 values are accurate. If so, and if the reports of 31P ATP T2 values in excess of 60 ms at lower field strengths are to be accepted (4-7), then there is indeed a pronounced reduction of T2 values at ultrahigh field strengths, despite the authors' conclusion that there is “…no clear field dependence… (p. 203).”
Knowledge of ultrahigh field 31P ATP T2 values will be critical for determining optimal sequence design strategies and sequence parameters as well for assessing fundamental mechanisms influencing ATP relaxation such as diffusion, susceptibility effects, etc. Unfortunately, there are some puzzling aspects of the measurements and/or interpretations of these values in the recent report by Lei et al. (1) which can hopefully be clarified. Simply put, is the history of 31P ATP T2 measurements at lower field strengths repeating itself (2-7) or is there a fundamental shortening of 31P ATP T2 values at ultrahigh field strengths?
