Investigating the regional effect of the chemical shift displacement artefact on the J-modulated lactate signal at ultra high-field.

The present work aims to show the applicability of an analytical model for the optimisation of the STEAM sequence timing parameters for lactate detection at ultra high-field. The effects of the chemical shift displacement artefact on the J-modulated signal for a weakly-coupled spin system were considered in the three applied directions of field gradients and the product operator formalism was used to obtain expressions for the signal modulation in each compartment of the excited volume. The validity of this model was demonstrated experimentally at 7 T in a phantom and acquisitions with optimised parameters were performed on a healthy volunteer. The spectra acquired with TE = 144 ms with the optimised mixing time and TE = 288 ms showed easily detectable lactate peaks in the normal human brain. Additionally, the acquisition with the longer TE resulted in a spectrum with less lipid/macromolecular contamination. The simulations shown here demonstrated that the proposed analytical model is suitable for correctly predicting the resulting lactate signal. With the optimised parameters, it was possible to use a simple sequence with sufficient signal-to-noise ratio to reliably distinguish lactate from overlapping resonances in a healthy brain.

Simplifying LR-HSQC spectra using a triple-quantum filter: The LR-HTQC experiment.

Long-range heteronuclear single quantum correlation (LR-HSQC) experiments may be applied for detecting long-range correlations but suffer from two disadvantages, common to all heteronuclear long-range correlation experiments: (i) The information density in LR-HSQC spectra may be too high to be used directly without "filtering out" shorter range correlations, and (ii) often, substantial differences in intensity among cross peaks exist, potentially hampering the visualization of weak, often crucial cross peaks. In this contribution, we propose a modified LR-HSQC experiment, the LR-HTQC experiment (Long-Range Heteronuclear Triple Quantum Correlation) that partially solves the problems aforementioned. We show theoretically and experimentally that the LR-HTQC experiment removes the intense cross peaks of CH spin pairs, substantially reduces the medium intensity of cross peaks originating from CHH' spin systems, whereas the typically weak intensity of cross peaks of CHH'H″ and C(H)n, n > 3 spin systems is less affected. Consequently, the LR-HTQC experiment affords simplified long-range heteronuclear shift correlation spectra and scales down large intensity differences among different types of cross peaks, although a certain general reduction of signal intensities has to be accepted.

D-HMBC versus LR-HSQMBC: Which experiment provides theoretically and experimentally the best results?

The long-range heteronuclear single quantum multiple bond correlation (LR-HSQMBC) experiment is the experiment of choice for visualizing heteronuclear long-range coupling interactions n JCH across 4-6-bonds and is experimentally superior to the decoupled heteronuclear multiple-bond correlation (D-HMBC) experiment. Yet, the exact reasons have not been fully understood and established. On the basis of our recent investigation of the nonrefocused variants LR-HSQC and HMBC, we have extended a JHH' -dedicated investigation to the D-HMBC and LR-HSQMBC experiments. Unlike the nonrefocused variants, the influence of homonuclear couplings JHH' on the intensity of long-range n JCH cross-peaks is not easily predictable and may be summarized as follows: (a) irrespective of the magnitude and number of JHH' interactions long-range n JCH cross-peaks are more intense in D-HMBC spectra as long as the evolution delay Δ is not too large, because in contrast to LR-HSQMBC no JHH' -caused intensity zeroes will occur. (b) If JHH' is small and Δ large, the intensity of cross peaks in D-HMBC spectra may be weakened or may even vanish at Δ = (0.25+0.5k)/JHH ', whereas for the LR-HSQMBC this unwanted effect occurs at Δ = k + 0.5/JHH' . Consequently, when Δ is adjusted to visualize weak n JCH long-range correlations, our findings corroborate that there are potentially more cross-peaks expected to show up in a LR-HSQMBC spectrum compared with a D-HMBC spectrum. This has been indeed noticed experimentally, even though the intensity of a many long-range n JCH cross-peaks may still be higher in the spectra of the D-HMBC experiment correspondingly adjusted for detecting weak n JCH correlations.

Measurement of long-range heteronuclear coupling constants using the peak intensity in classical 1D HMBC spectra.

In this contribution, we show that the magnitude of heteronuclear long-range coupling constants can be directly extracted from the classical 1D HMBC spectra, as all multiplet lines of a cross-peak always and exclusively vanish for the condition Δ = k/n JCH . To the best of our knowledge, this feature of the classical HMBC has not yet been noticed and exploited. This condition holds true, irrespective of the magnitude and numbers of additional active and passive homonuclear n JHH' couplings. Alternatively, the n JCH value may also be evaluated by fitting the peak's intensity in the individual spectra to its simple sin(πn JCH Δ)exp(-Δ/T2eff ) dependence. Compared to the previously proposed J-HMBC sequences that also use the variation of the cross-peak's intensity for extracting the coupling constants, the classical HMBC pulse sequence is significantly more sensitive.

Why is HMBC superior to LR-HSQC? Influence of homonuclear couplings JHH' on the intensity of long-range correlations.

Long-range heteronuclear single quantum correlation (LR-HSQC) experiments may be applied as an alternative to heteronuclear multiple-bond correlation (HMBC) experiments for detecting long-range correlations but has never enjoyed popularity for that purpose. To the best of our knowledge, the exact reasons have not yet been fully established. For both experiments, it is widely accepted that the evolution of proton-proton homonuclear couplings JHH' during the polarization transfer delays Δ leads to significant losses, and that the intensity of the observable coherence is zero when JHH' matches the condition Δ = 0.5/JHH' . Here, we analyze the influence of JHH' on the intensity of long-range correlations in HMBC and LR-HSQC spectra. We show that for both experiments long-range correlations will not be canceled because of homonuclear couplings JHH' . Our theoretical and experimental results definitely establish and validate the superiority of HMBC-based experiments among the family of heteronuclear long-range correlation experiments: (a) the overall cross peak's intensity is higher, and (b) in LR-HSQC experiments, the intensity of the long-range cross peaks is additionally influenced in an unwanted way by the magnitude and number of passive homonuclear proton-proton couplings JHH' .

Coherence pathway analysis of J-coupled lipids and lactate and effective suppression of lipids upon the selective multiple quantum coherence lactate editing sequence.

Objective.The selective multiple quantum coherence (Sel-MQC) sequence is a magnetic resonance spectroscopy (MRS) technique used to detect lactate and suppress co-resonant lipid signalsin vivo. The coherence pathways of J-coupled lipids upon the sequence, however, have not been studied, hindering a logical design of the sequence to fully attenuate lipid signals. The objective of this study is to elucidate the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and find a strategy to effectively suppress lipid signals from these pathways while keeping the lactate signal.Approach.The product operator formalism was used to express the evolutions of the J-coupled spins of lipids and lactate. The transformations of the product operators by the spectrally selective pulses of the sequence were calculated by using the off-resonance rotation matrices. The coherence pathways and the conversion rates of the individual pathways were derived from them. Experiments were performed on phantoms and two human subjects at 3 T.Main results.The coherence pathways contributing to the various lipid resonance signals by the Sel-MQC sequence depending on the gradient ratios and RF pulse lengths were identified. Theoretical calculations of the signals from the determined coherence pathways and signal attenuations by gradients matched the experimental data very well. Lipid signals from fatty tissues of the subjects were successfully suppressed to the noise level by using the gradient ratio -0.8:-1:2 or 1:0.8:2. The new gradient ratios kept the lactate signal the same as with the previously used gradient ratio 0:-1:2.Significance.The study has elucidated the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and demonstrated how lipid signals can be effectively suppressed while keeping lactate signals by using information from the coherence pathway analysis. The findings enable applying the Sel-MQC sequence to lactate detection in an environment of high concentrations of lipids.