7 tricks for 7 T CEST: Improving the reproducibility of multipool evaluation provides insights into the effects of age and the early stages of Parkinson's disease

• Published in: NMR in biomedicine Vol. 36; no. 6; pp. e4717 - n/a
• Main Authors: Mennecke, Angelika, Khakzar, Katrin M., German, Alexander, Herz, Kai, Fabian, Moritz S., Liebert, Andrzej, Blümcke, Ingmar, Kasper, Burkhard S., Nagel, Armin M., Laun, Frederik B., Schmidt, Manuel, Winkler, Jürgen, Dörfler, Arnd, Zaiss, Moritz
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2023
• Subjects: 7 T; age; Age differences; Age factors; Aliphatic compounds; amide; Amides; Amplitudes; Biological products; Brain; CEST; Coefficient of variation; Humans; Interpolation; Lorentzian fitting; Magnetic Resonance Imaging - methods; Movement disorders; Neurodegenerative diseases; Neuroimaging; Noise reduction; Optimization; Overhauser effect; Parkinson; Parkinson Disease - diagnostic imaging; Parkinson's disease; Principal components analysis; Reproducibility; Reproducibility of Results; rNOE; Smoothing; standardization; Substantia nigra; amide; 7 T; Lorentzian fitting; rNOE; standardization; CEST; Parkinson; age
• DOI: 10.1002/nbm.4717
• ISSN: 0952-3480; 1099-1492

The objective of the current study was to optimize the postprocessing pipeline of 7 T chemical exchange saturation transfer (CEST) imaging for reproducibility and to prove this optimization for the detection of age differences and differences between patients with Parkinson's disease versus normal subjects. The following 7 T CEST MRI experiments were analyzed: repeated measurements of a healthy subject, subjects of two age cohorts (14 older, seven younger subjects), and measurements of 12 patients with Parkinson's disease. A slab‐selective, B1+‐homogeneous parallel transmit protocol was used. The postprocessing, consisting of motion correction, smoothing, B0‐correction, normalization, denoising, B1+‐correction and Lorentzian fitting, was optimized regarding the intrasubject and intersubject coefficient of variation (CoV) of the amplitudes of the amide pool and the aliphatic relayed nuclear Overhauser effect (rNOE) pool within the brain. Seven “tricks” for postprocessing accomplished an improvement of the mean voxel CoV of the amide pool and the aliphatic rNOE pool amplitudes of less than 5% and 3%, respectively. These postprocessing steps are: motion correction with interpolation of the motion of low‐signal offsets (1) using the amide pool frequency offset image as reference (2), normalization of the Z‐spectrum using the outermost saturated measurements (3), B0 correction of the Z‐spectrum with moderate spline smoothing (4), denoising using principal component analysis preserving the 11 highest intensity components (5), B1+ correction using a linear fit (6) and Lorentzian fitting using the five‐pool fit model (7). With the optimized postprocessing pipeline, a significant age effect in the amide pool can be detected. Additionally, for the first time, an aliphatic rNOE contrast between subjects with Parkinson's disease and age‐matched healthy controls in the substantia nigra is detected. We propose an optimized postprocessing pipeline for CEST multipool evaluation. It is shown that by the use of these seven “tricks”, the reproducibility and, thus, the statistical power of a CEST measurement, can be greatly improved and subtle changes can be detected. The presented postprocessing pipeline provides increased homogeneity and reproducibility. The mean voxel CoV is decreased to less than 5% for amide and to less than 3% for aliphatic rNOE contrast. Healthy aging‐related changes and altered aliphatic rNOE pools in the substantia nigra of patients in the early stages of Parkinson's disease are detected.