Achieva 3t x

Magnetic resonance imaging (MRI) was performed on a 3T MR scanner (Philips Achieva 3T X) using a 32‐channel head coil. All participants were instructed to lay still throughout the complete scanning time, and the head was padded with cushions to reduce movement during scanning. Diffusion‐weighted imaging was performed using 60 diffusion‐weighted gradient directions (b = 1,000 s/mm²) with six interleaved non‐diffusion‐weighted image, yielding a total acquisition time of approximately ten minutes (FOV = 224 × 224 × 120 mm³, 2 × 2 × 2 mm³ voxel size, 60 slices, TR = 8,151 ms, TE = 88 ms). In addition, a high resolution MPRAGE T1‐weighted image was acquired as a reference for EPI‐distortion correction (FOV 256 × 256 × 220 mm³, 1 × 1 × 1 mm³ voxel size, TR = 8.3 ms, TE = 3.8 ms, 9° flip angle).

On the first day of Visit 4 and 7, at 3:00 P.M., in vivo IMCL content in tibialis anterior muscle was assessed by ¹H-MRS on a 3.0 T whole-body magnetic resonance system (Achieva 3Tx; Philips Healthcare) as described previously [29 (link)]. Subsequently, in vivo mitochondrial oxidative capacity was determined by ³¹P-MRS at 4:00 P.M., as previously described [30 (link)]. On a separate day, at the last day of the end-of-treatment visits (to prevent effects of exercise testing on the other outcome parameters), acetylcarnitine concentrations were acquired by ¹H-MRS in skeletal muscle before and after exercise. Participants were fasted from 12:00 A.M. and were asked to refrain from strenuous physical activity 72 h before the measurement. Detailed descriptions of the different MRS measurement procedures can be found in the supplemental materials.

On day 15 at 6:30 a.m. after an overnight fast, hepatic glycogen was determined by 13C-MRS. All 13C-MRS experiments were performed on a 3T MR system (Achieva 3T-X Philips Healthcare, Best, The Netherlands) using a 21 × 24 cm 13C quadrature detection surface coil (RAPID Biomedical GmbH, Rimpar, Germany). Hepatic glycogen levels were measured as described previously [24 (link)] by acquiring 13C MR spectra (Free induction decay, using block pulses calibrated to reach a 90-degree pulse at an 8 cm depth; TR: 280 ms; NSA: 4096). Data analysis was performed with an in-house-developed Matlab script including automatic postprocessing and integration of spectra and corrections for the coil sensitivity profile, as reported before [24 (link)]. Liver volume was measured directly after the hepatic glycogen measurements by MRI. Analyses were performed manually on cross-sectional MRI images in MATLAB. Relative changes in glycogen arbitrary units (AUs) between the high-GI/SFA and low-GI/SFA measurement ((hepatic glycogen low GI/SFA − hepatic glycogen high GI/SFA)/hepatic glycogen high GI/SFA × 100) were calculated and are reported in the results section as a single value for the relative change between high and low GI/SFA. Total hepatic glycogen was calculated as the hepatic glycogen × liver volume.

Brain MRI was performed in patients with the most severe and persistent delirium (> 3 days during ICU stay) and/or abnormal neurological examination. Brain MRI was only feasible if patients were hemodynamically stable (i.e., patients without catecholamines) and non-hypoxemic (FiO₂ < 40% and PEEP < 8 or < 4 L/min oxygen) and without contra-indication to MRI. Patients underwent a gadolinium-enhanced brain MRI on a 3T MRI scanner (Achieva 3Tx, Philips, Best, The Netherlands, or SIGNA HDX 3T, GE, Milwaukee, USA). Acquisition parameters are summarized in Additional file 1.