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, ‐homogeneous parallel transmit protocol was used. The postprocessing, consisting of motion correction, smoothing, ‐correction, normalization, denoising, ‐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), correction of the Z‐spectrum with moderate spline smoothing (4), denoising using principal component analysis preserving the 11 highest intensity components (5), 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.

Background: Epilepsy surgery for focal cortical dysplasia type II (FCD II) offers good chances for seizure freedom, but remains a challenge with respect to lesion detection, defining the epileptogenic zone and the optimal resection strategy. Integrating results from magnetic source imaging from magnetoencephalography (MEG) with magnetic resonance imaging (MRI) including MRI postprocessing may be useful for optimizing these goals. Methods: We here present data from 21 adult FCD II patients, investigated during a 10 year period and evaluated including magnetic source imaging. 16 patients had epilepsy surgery, i.e. histopathologically verified FCD II, and a long follow up. We present our analysis of epileptogenic zones including MEG in relation to structural data according to MRI data and relate these results to surgical outcomes. Results: FCD II in our cohort was characterized by high MEG yield and localization accuracy and MEG showed impact on surgical success-rates. MEG source localizations were detected in 95.2% of patients and were as close as 12.3 +/- 8,1mm to the MRI-lesion. After a mean follow up of > 3 years, we saw > 80% Engel I outcomes, with more favourable outcomes when the MEG source was completely resected (Fishers exact test 0,033). Conclusion: We argue for a high value of conducting a combined MEG-MRI approach in the presurgical workup and the resection strategy in patients with FCD II related epilepsy.

Purpose: In this work, we investigated the ability of neural networks to rapidly and robustly predict Lorentzian parameters of multi‐pool CEST MRI spectra at 7 T with corresponding uncertainty maps to make them quickly and easily available for routine clinical use.Methods: We developed a deepCEST 7 T approach that generates CEST contrasts from just 1 scan with robustness against B₁ inhomogeneities. The input data for a neural feed‐forward network consisted of 7 T in vivo uncorrected Z‐spectra of a single B₁ level, and a B₁ map. The 7 T raw data were acquired using a 3D snapshot gradient echo multiple interleaved mode saturation CEST sequence. These inputs were mapped voxel‐wise to target data consisting of Lorentzian amplitudes generated conventionally by 5‐pool Lorentzian fitting of normalized, denoised, B₀‐ and B₁‐corrected Z‐spectra. The deepCEST network was trained with Gaussian negative log‐likelihood loss, providing an uncertainty quantification in addition to the Lorentzian amplitudes.Results: The deepCEST 7 T network provides fast and accurate prediction of all Lorentzian parameters also when only a single B₁ level is used. The prediction was highly accurate with respect to the Lorentzian fit amplitudes, and both healthy tissues and hyperintensities in tumor areas are predicted with a low uncertainty. In corrupted cases, high uncertainty indicated wrong predictions reliably.Conclusion: The proposed deepCEST 7 T approach reduces scan time by 50% to now 6:42 min, but still delivers both B₀‐ and B₁‐corrected homogeneous CEST contrasts along with an uncertainty map, which can increase diagnostic confidence. Multiple accurate 7 T CEST contrasts are delivered within seconds.

Purpose: To enable whole‐brain quantitative CEST MRI at ultra‐high magnetic field strengths (B₀ ≥ 7T) within short acquisition times.Methods: Multiple interleaved mode saturation (MIMOSA) was combined with fast online‐customized (FOCUS) parallel transmission (pTx) excitation pulses and correction to achieve homogenous whole‐brain coverage. Examinations of 13 volunteers were performed on a 7T MRI system with 3 different types of pulse sequences: (1) saturation in circular polarized (CP) mode and CP mode readout, (2) MIMOSA and CP readout, and (3) MIMOSA and FOCUS readout. For comparison, the inverse magnetic transfer ratio metric for relayed nuclear Overhauser effect and amide proton transfer were calculated. To investigate the number of required acquisitions for a good correction, 4 volunteers were measured with 6 different B₁ amplitudes. Finally, time point repeatability was investigated for 6 volunteers.Results: MIMOSA FOCUS sequence using correction, with both single and multiple points, reduced inhomogeneity of the CEST contrasts around the occipital lobe and cerebellum. Results indicate that the most stable inter‐subject coefficient of variation was achieved using the MIMOSA FOCUS sequence. Time point repeatability of MIMOSA FOCUS with single‐point correction showed a maximum coefficient of variation below 8% for 3 measurements in a single volunteer.Conclusion: A combination of MIMOSA FOCUS with a single‐point correction can be used to achieve quantitative CEST measurements at ultra‐high magnetic field strengths. Compared to previous correction methods, acquisition time can be reduced as additional scans required for correction can be omitted.

Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel FA2H variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity.