Water-suppression cycling 3-T cardiac 1 H-MRS detects altered creatine and choline in patients with aortic or mitral stenosis

Abstract

Cardiac proton spectroscopy (¹ H-MRS) is widely used to quantify lipids. Other metabolites (e.g. creatine and choline) are clinically relevant but more challenging to quantify because of their low concentrations (approximately 10 mmol/L) and because of cardiac motion. To quantify cardiac creatine and choline, we added water-suppression cycling (WSC) to two single-voxel spectroscopy sequences (STEAM and PRESS). WSC introduces controlled residual water signals that alternate between positive and negative phases from transient to transient, enabling robust phase and frequency correction. Moreover, a particular weighted sum of transients eliminates residual water signals without baseline distortion. We compared WSC and the vendor's standard 'WET' water suppression in phantoms. Next, we tested repeatability in 10 volunteers (seven males, three females; age 29.3 ± 4.0 years; body mass index [BMI] 23.7 ± 4.1 kg/m² ). Fat fraction, creatine concentration and choline concentration when quantified by STEAM-WET were 0.30% ± 0.11%, 29.6 ± 7.0 μmol/g and 7.9 ± 6.7 μmol/g, respectively; and when quantified by PRESS-WSC they were 0.30% ± 0.15%, 31.5 ± 3.1 μmol/g and 8.3 ± 4.4 μmol/g, respectively. Compared with STEAM-WET, PRESS-WSC gave spectra whose fitting quality expressed by Cramér-Rao lower bounds improved by 26% for creatine and 32% for choline. Repeatability of metabolite concentration measurements improved by 72% for creatine and 40% for choline. We also compared STEAM-WET and PRESS-WSC in 13 patients with severe symptomatic aortic or mitral stenosis indicated for valve replacement surgery (10 males, three females; age 75.9 ± 6.3 years; BMI 27.4 ± 4.3 kg/m² ). Spectra were of analysable quality in eight patients for STEAM-WET, and in nine for PRESS-WSC. We observed comparable lipid concentrations with those in healthy volunteers, significantly reduced creatine concentrations, and a trend towards decreased choline concentrations. We conclude that PRESS-WSC offers improved performance and reproducibility for the quantification of cardiac lipids, creatine and choline concentrations in healthy volunteers at 3 T. It also offers improved performance compared with STEAM-WET for detecting altered creatine and choline concentrations in patients with valve disease.

Keywords: 1H-MRS; 3 T; PRESS; STEAM; cardiac; heart; human; water-suppression cycling.

FIGURE 1

Explanation of the water‐suppression cycling (WSC) ¹H‐MRS approach. A, Simplified pulse diagram showing the difference in water suppression between odd‐ and even‐numbered transients. B, Top: frequency domain plots of simulated example odd and even transients; bottom: the average of these; inset: zoom to show metabolite signal amplitudes. C, Equivalent plots after per‐transient frequency and phase correction based on the residual water peak. D, Equivalent plots with per‐transient frequency and phase correction and weighting according to Equation 2. The final WSC spectrum is shown at the bottom right. Note that a green dashed line is plotted at the same vertical position in all three columns to illustrate that the WSC processing preserves metabolite peak amplitudes

FIGURE 2

Voxel position (white box) as shown on a short‐axis view (left) and a horizontal long axis view (right)

FIGURE 3

Correlation of measured creatine (Cr) concentration and the actual Cr concentration in each phantom compartment measured with A, PRESS‐WSC, B, STEAM‐WET, C, PRESS‐WSC and D, STEAM‐WSC. An anomalous point in A has been identified and labelled using a black cross. This point was subsequently excluded from data analysis. RMSE, root‐mean‐squared error

FIGURE 4

Spectra from a single volunteer comparing all four protocols tested in the volunteer study

FIGURE 5

Comparision of Cramér‐Rao lower bounds (CRLB) and signal‐to‐noise ratio (SNR) across all four protocols tested in the volunteer study for A and D, lipids, B and E, creatine and C and F, choline. The black cross and the attached whiskers represent the median and the interquartile across all healthy volunteers. For each plot, Wilcoxon signed‐rank tests were conducted across all six possible pairs and all significant p‐values (p ≤ 0.05) are shown

FIGURE 6

Comparison of metabolite concentrations and fat fractions in healthy and patient cohort with STEAM‐WET‐150 (‘o’) and PRESS‐WSC (‘×’) for A, lipids, B, creatine and C, choline against various published literature values. For healthy volunteers, the values are an average between scan 1 and scan 2 while literature data are taken from the following sources: Rial et al. (α), ³ Mahmod et al. (β), ⁷³ Nakae et al. (γ) ⁵⁰ and Gilinder et al. (δ). ⁶ Data from Rial et al. and Mahmod et al. were obtained at 3 T, while Nakae et al. and Gilinder et al. obtained their data at 1.5 T. For the current study, data points more than 1.5 interquartile ranges above the upper quartile or below the lower quartile are treated as outliers (denoted in black). The black cross and the attached whiskers represent the mean and the standard deviations across all healthy volunteers. The p‐values from the unpaired Student's t‐tests are also provided. AS, aortic stenosis; CHF, chronic heart failure

FIGURE 7

Bland–Altman plots: A, for lipids with STEAM‐WET‐150 (coefficient of repeatability [CR] = 0.22%) and PRESS‐WSC (CR = 0.24%); B, for creatine with STEAM‐WET‐150 (CR = 15.1 μmol/g) and PRESS‐WSC (CR = 4.19 μmol/g); and C, for choline with STEAM‐WET‐150 (CR = 3.2 μmol/g) and PRESS‐WSC (CR = 1.92 μmol/g). The mean difference and the limits of agreement are shown. Data points more than 1.5 interquartile ranges above the upper quartile or below the lower quartile are treated as outliers (coloured black)

FIGURE 8

Spectra from a healthy volunteer (left, both A and C) compared with that of a patient (right, both B and D) suffering from aortic stenosis. The spectra were acquired with PRESS‐WSC in a healthy volunteer (A) and a patient (B), and with STEAM‐WET‐150 in a healthy volunteer (C) and a patient (D). All spectra are scaled by the corresponding water peak amplitude. A decrease in creatine (Cr) is seen between these pairs