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Purpose To develop a novel sequence for simultaneous quantification of T1 and T2 relaxation times in the myocardium based on the transient phase of the balanced steady-state free precession. Methods A new prototype sequence, named ' cardiac balanced-SSFP inversion recovery with interleaved sampling acquisition' (CABIRIA) was developed based on a single-shot bSSFP readout following an inversion pulse. With this method, T1 and T2 values can be calculated from the analysis of signal evolution. The scan duration for a single slice in vivo was 8 heartbeats, thus feasible in a breath-hold. The sequence was validated both in vitro by comparing it to conventional inversion recovery and multi-echo spin-echo methods and in 5 healthy volunteers by comparing it to the Modified Look-Locker Inversion Recovery (MOLLI) sequence and to a T2 quantification sequence based on multi-T2-prepared bSSFP. Results The method showed good agreement with conventional methods for both T1 and T2 measurements (concordance correlation coefficient ≥ 0.99) in vitro. In healthy volunteers the measured T1 values were 1227 ± 68 ms and T2 values 37.9 ± 2.4 ms, with similar inter- and intrasubject variability with respect to existing methods. Conclusion The proposed CABIRIA method enables simultaneous quantification of myocardial T1 and T2 values with good accuracy and precision. Magn Reson Med 74:365-371, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: This study compares the performance and the reproducibility of quantitative T2, T2* and the magnetisation transfer ratio (MTR) of articular cartilage at 7T and 3T.Methods: Axial MRI of the patella was performed in 17 knees of healthy volunteers (25.8 ± 5.7 years) at 3T and 7T using a comparable surface coil and whole-body MR systems from the same vendor, side-by-side. Thirteen knee joints were assessed once, and four knee joints were measured three times to assess reproducibility. T2 relaxation was prepared by a multi-echo, spin-echo sequence and T2* relaxation by a multi-echo, gradient-echo sequence. MTR was based on a magnetisation transfer-sensitized, steady-state free precession approach. Statistical analysis-of-variance and coefficient-of-variation (CV) were prepared.Results: For T2 and T2*, global values were significantly lower at 7T compared with 3T; the zonal evaluation revealed significantly less pronounced stratification at 7T (p < 0.05). MTR provided higher values at 7T (p < 0.05). CV, indicating reproducibility, showed slightly lower values at 7T, but only for T2 and T2*.Conclusion: Although lower T2 and T2* relaxation times were expected at 7T, the differences in stratification between the field strengths were reported for the first time. The assessment of MT is feasible at 7T, but requires further investigation. [ABSTRACT FROM AUTHOR]

Balanced steady-state free precession (bSSFP) suffers from a considerable signal loss in tissues. This apparent signal reduction originates from magnetization transfer (MT) and may be reduced by an increase in repetition time or by a reduction in flip angle. In this work, MT effects in bSSFP are modulated by a modification of the bSSFP sequence scheme. Strong signal attenuations are achieved with short radio frequency (RF) pulses in combination with short repetition times, whereas near full, i.e., MT-free, bSSFP signal is obtained by a considerable prolongation of the RF pulse duration. Similar to standard methods, the MT ratio (MTR) in bSSFP depends on several sequence parameters. Optimized bSSFP protocol settings are derived that can be applied to various tissues yielding maximal sensitivity to MT while minimizing contribution from other impurities, such as off-resonances. Evaluation of MT in human brain using such optimized bSSFP protocols shows high correlation with MTR values from commonly used gradient echo (GRE) sequences. In summary, a novel method to generate MTR maps using bSSFP image acquisitions is presented and factors that optimize and influence this contrast are discussed. Magn Reson Med 58:511-518, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In this work, the effects of susceptibility variation from dilute, micron-sized spherical field perturbers and diffusion on balanced steady-state free precession (bSSFP) are analyzed. Predictions from Monte Carlo simulations are in good agreement with experiments and reveal that, for diffusing protons, susceptibility variation becomes apparent as a reduction in the overall bSSFP signal intensity. This reduction depends on microsphere parameters (radius and susceptibility difference), as well as on sequence-related parameters (repetition time and flip angle) and on relaxation times. Specific Monte Carlo results from one set of parameter values can be extrapolated to another set of values by means of a scaling law and a substitution model. The scaling law, derived from the Bloch-Torrey equation, captures the dependencies of bSSFP signal reduction on susceptibility and diffusion-related changes and on repetition time, whereas the substitution model describes those on flip angle and relaxation times. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction Stereotactic body radiation therapy (SBRT) has been validated for liver lesions [1]. Because high dose per fraction is delivered on small volume, very accurate lesion segmentation is necessary. MRI is the most relevant imaging for liver lesion contouring but it is prone to motion artifacts if breathing is not managed. Evaluation of liver lesion motion induced by breathing is necessary in radiotherapy to guide patient treatment planning (respiratory gating). A 4D-MRI sequence was previously validated for liver [2]. In this study, an automated method was developed to sort images according to the breathing cycle. Methods The 4D-MRI acquisition is performed with an experimental sequence (bSSFP TrueFISP [3]) on 1.5T Magnetom AeraTM (Siemens). This sequence allows very fast axial and sagittal 2D acquisition during free breathing. Axial slice positions (0.88 s/slice) are incremented to cover the liver volume. Sagittal slices (navigators) are acquired at a fixed position. The navigators are used to assign a phase for each axial slice which depend on an amplitude sequencing of the respiratory cycle (0% = inspiration, 16%, 33%, 50% = expiration, 66%, 83%). Lung volume is estimated on each navigator by automatic segmentation and allows to assign a phase for the coupled axial image in the breathing cycle. As the image number per respiratory cycle is low, the sequence is repeated 20 times in order to achieve satisfactory sampling. The sequence was evaluated on 4 volunteers with an audio coaching (5 and 6 s period) and 2 patients without audio coaching. Results Patient image sorting according to their position in the breathing cycle was realized by automated phase detection (Fig. 1) and images were imported into the treatment planning system Eclipse 13.7TM (Varian) in 6 phases. Audio coaching is not used here. It is required for patients with irregular breathing cycle. From axial images, Eclipse reconstructs slices in sagittal and coronal plans, and allows to display a cine view with the 6 breathing phases in order to analyze the dynamic behavior of the liver. Conclusions 4D-MRI images from volunteers and patients were acquired with bSSFP TrueFISP sequence. After automated sorting with the method developed in this study, 6 breathing cycle phases were imported into Eclipse. Patient 4D-MRI can be registered with 4D-CT to increase the physician's segmentation accuracy. [ABSTRACT FROM AUTHOR]

Introduction Liver imaging is challenging due to its constant movement with breathing. In Magnetic Resonance Imaging (MRI), different strategies have been developed for organ movement consideration [1–3] . These methods are limited by the temporal resolution, as well as image quality. A novel retrospective gating method for dynamic 3D MR imaging during free breathing was developed [1] and further improved by Celicanin et al. [4] . This work aims of assessing the method and the reconstruction technique for liver cases. The final clinical application is to improve liver lesion delineation for Stereotactic Body Radiation Therapy (SBRT). Methods The innovative 4D MRI approach has been evaluated for liver motion estimation during entire respiratory cycle on a healthy volunteer. It is based on simultaneous acquisition of 2D images and a navigator set using acceleration CAIPIRINHA technique [4] providing no temporal divergence between them. During the entire acquisition time, the navigator is fixed in the same position, while the image position is changing, in order to cover the entire organ during free breathing [1] . The entire respiratory cycle is acquired, using a modified balanced Steady State Free Precession sequence (bSSFP) and is reconstructed in a retrospective manner ( Fig. 1 ). Images are acquired with a 1.5T MRI (MAGNETOM Aera; Siemens Medical Solutions, Erlangen, Germany), using an 18-channel design body flex coil. The 3.5 mm 2D axial slices are obtained, using the following sequence parameters: TE = 2.27 ms, TR = 591.97 ms, FA = 70 °, FOV = 37 × 37 cm 2 , matrix = 256 × 246. Total acquisition time is 33.175 s (0.83 s per slice). Results The preliminary results obtained on a healthy volunteer are shown in Fig. 1 . Images are characterized by high resolution and great contrast, making this method promising for liver lesion examination. The reconstruction of 4D MRI and the sequence optimization to cover the entire respiration cycle with the appropriate time sampling is ongoing work. Conclusions The benefit of MRI acquisition in treatment position to improve lesion contouring for liver SBRT has already been demonstrated [5] . The presented 4D MRI method represents a highly time efficient technique for the free breathing liver motion registration, giving the possibility to sort and reconstruct the images according to the respiratory phases. It will allow registration with 4D CT planning, likely to improve delineation accuracy. The same approach can be applied to study moving organs others than liver. [ABSTRACT FROM AUTHOR]

Poster: Physics track: Quantitative functional and biological imaging PO-1687: Regional lung motion amplitude and variability assessment from a 4DMRI dataset E. Colvill, S. Safai, O. Bieri, S. Kozerke, D.C. Weber, A. Lomax, G. Fattori. [Extracted from the article]

Aim: To assess cartilage quality using delayed gadolinium-enhanced magnetic resonance imaging after repair of osteochondral lesions of the talus using autologous matrix-induced chondrogenesis (AMIC). Materials and methods: A three-dimensional (3D) spoiled gradient-echo (SGE) sequence at 3 T was used to obtain quantitative T1 relaxation times before and after Gd-DTPA2 (Magnevist, 0.2 mM/kg bod weight) administration to assess 23 cases of AMIC-aided repair of osteochondral lesions of the talus. Delta relaxation rates (ΔR1) for reference cartilage (RC) and repair tissue (RT), and the relative delta relaxation rate (rΔR1) were calculated. The morphological appearance of the cartilage RT was graded on sagittal dual-echo steady-state (DESS) views according to the “magnetic resonance observation of cartilage repair tissue” (MOCART) protocol. The study was approved by the institutional review board and written consent from each patient was obtained. Results: The AMIC cases had a mean T1 relaxation time of 1.194 s (SD 0.207 s) in RC and 1.470 s (SD 0.384 s) in RT before contrast medium administration. The contrast-enhanced T1 relaxation time decreased to 0.480 s (SD 0.114 s) in RC and 0.411 s (SD 0.096 s) in RT. There was a significant difference (p > 0.05) between the ΔR1 in RC (1.372 × 10−3/s, range 0.526–3.201 × 10−3/s, SD 0.666 × 10−3/s) and RT (1.856 × 10−3/s, range 0.93–3.336 × 10−3/s, SD 0.609 × 10−3/s). The mean rΔR1 was 1.49, SD 0.45). The mean MOCART score at follow-up was 62.6 points (range 30–95, SD 15.3). Conclusion: The results of the present study suggest that repair cartilage resulting from AMIC-aided repair of osteochondral lesions of the talus has a significantly lower glycosaminoglycan (GAG) content than normal hyaline cartilage, but can be regarded as having hyaline-like properties. [ABSTRACT FROM AUTHOR]

Proffered Papers: Proffered papers 30 - Protons and ions OC-0578: Ultrasound-guided PBS proton beam tracking in lung using a statistical motion model M. Krieger, A. Giger, A. Duetschler, C. Jud, P.C. Cattin, R.V. Salomir, O. Bieri, D.C. Weber, A.J. Lomax, Y. Zhang. [Extracted from the article]

Objective: To demonstrate the potential of a double angle stimulated echo (DA-STE) method for fast and accurate "full" homogeneous Helmholtz-based electrical properties tomography using a simultaneous B 1 + magnitude and transceive phase measurement., Methods: The combination of a spin and stimulated echo can be used to yield an estimate of both B 1 + magnitude and transceive phase and thus provides the means for "full" EPT reconstruction. An interleaved 2D acquisition scheme is used for rapid acquisition. The method was validated in a saline phantom and compared to a double angle method based on two single gradient echo acquisitions (GRE-DAM). The method was evaluated in the brain of a healthy volunteer., Results: The B 1 + magnitude obtained with DA-STE showed excellent agreement with the GRE-DAM method. Conductivity values based on the "full" EPT reconstruction also agreed well with the expectations in the saline phantom. In the brain, the method delivered conductivity values close to literature values., Discussion: The method allows the use of the "full" Helmholtz-based EPT reconstruction without the need for additional measurements. As a result, quantitative conductivity values are improved compared to phase-based EPT reconstructions. DA-STE is a fast complex- B 1 + mapping technique that could render EPT clinically relevant at 3 T., Competing Interests: Declaration. Conflict of interest: The authors have no conflict of interest to declare. Ethical approval: In vivo experiments were approved by the local ethics committee, and informed written consent was obtained from all participants prior to the study., (© 2024. The Author(s).)

Purpose: To establish an interleaved multislice variant of the averaged magnetization inversion-recovery acquisitions (AMIRA) approach for 2D spinal cord imaging with increased acquisition efficiency compared with the conventional 2D single-slice approach(es), and to determine essential prerequisites for a working interleaved multislice AMIRA approach in practice., Methods: The general AMIRA concept is based on an inversion recovery-prepared, segmented, and time-limited cine balanced SSFP sequence, generating images of different contrast. For AMIRA imaging of multiple, independent slices in a 2D interleaved fashion, a slice loop within the acquisition loops was programmed. The former non-selective inversions were replaced with slice-selective inversions with user-definable slice thickness., Results: The thickness of the slice-selective inversion in 2D interleaved multislice AMIRA should be doubled compared with the manufacturer's standard setting to avoid an increased sensitivity to flow and pulsation effects particularly in the CSF. However, this solution also limits its practical applicability, as slices located at directly adjacent vertebrae cannot be imaged together. Successful interleaved two-slice AMIRA imaging for a "reference" in vivo protocol with 0.50 × 0.50 mm 2 in-plane resolution and 8-mm slice thickness is demonstrated, therefore halving its acquisition time per slice from 3 min down to 1.5 min., Conclusion: The investigated 2D interleaved two-slice AMIRA variant facilitates spinal cord imaging that maintains similar contrast and the same resolution as the conventional 2D single-slice AMIRA approach, but does so with a halved acquisition time., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To introduce and evaluate TrueLung, an automated pipeline for computation and analysis of free-breathing and contrast-agent free pulmonary functional magnetic resonance imaging., Materials and Methods: Two-dimensional time-resolved ultra-fast balanced steady-state free precession acquisitions were transferred to TrueLung, which included image quality checks, image registration, and computation of perfusion and ventilation maps with matrix pencil decomposition. Neural network whole-lung and lobar segmentations allowed quantification of impaired relative perfusion (R Q ) and fractional ventilation (R FV ). TrueLung delivered functional maps and quantitative outcomes, reported for clinicians in concise documents. We evaluated the pipeline using 1.5T data from 75 children with cystic fibrosis by assessing the feasibility of functional MR imaging, average scan time, and the robustness of the functional outcomes. Whole-lung and lobar segmentations were manually refined when necessary, and the impact on R Q and R FV was quantified., Results: Functional imaging was feasible in all included CF children without any dropouts. On average, 7.9 ± 1.8 (mean±SD) coronal slice positions per patient were acquired, resulting in a mean scan time of 6min 20s per patient. The whole pipeline required 20min processing time per subject. TrueLung delivered the functional maps of all the subjects for radiological assessment. Quality controlling maps and segmentations lasted 1min 12s per patient. The automated segmentations and quantification of whole-lung defects were satisfying in 88% of patients (97% of slices) and the lobar quantification in 73% (93% of slices). The segmentations refinements required 16s per patient for the whole-lung, and 2min 10s for the lobe masks. The relative differences in R FV and R Q between fully-automated and manually refined data were 0.7% (1.2%) and 2.0% (2.9%) for whole-lung quantification (median, [third quartile]), and excluding two outliers, 1.7% (3.9%) and 1.2% (3.8%) for the lobes, indicating the refinements could be potentially omitted in several patients., Conclusions: TrueLung quickly delivers functional maps and quantitative outcomes in an objective and standardized way, suitable for radiological and pneumological assessment with minimal manual input. TrueLung can be used for clinical research in cystic fibrosis and might be applied across various lung diseases., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background Radially sampled averaged magnetization inversion-recovery acquisition (rAMIRA) imaging shows hyperintensity in the lateral corticospinal tract (CST) in patients with motor neuron diseases. Purpose To systematically determine the accuracy of the lateral corticospinal tract sign for detecting patients with amyotrophic lateral sclerosis (ALS) at rAMIRA MRI. Materials and Methods This study included prospectively acquired data from participants in ALS and other motor neuron disease imaging studies at the University Hospital Basel, Switzerland. All participants underwent 3-T axial two-dimensional rAMIRA imaging at four cervical intervertebral disk levels. The lateral CST sign was defined as spinal cord white matter hyperintensity dorsolateral to the anterior horns, with higher signal intensity than in the dorsal columns on axial rAMIRA images. Marker accuracy was assessed in a study data set and in an independent validation data set. Postmortem rAMIRA imaging and histopathologic analysis were performed in one participant who died during the study. Results Participants with ALS (study data set: 38 participants [mean age, 61 years; IQR, 15 years], 22 male participants; validation data set: 10 participants [mean age, 61 years; IQR, 21 years], seven male participants), post-polio syndrome (study data set: 25 participants [mean age, 68 years; IQR, 8 years], 12 male participants), spinal muscular atrophy (study data set: 10 participants [mean age, 43 years; IQR, 14 years], eight male participants; validation data set: five participants [mean age, 38 years; IQR, 19 years], two male participants), and healthy control participants (study data set: 60 participants [mean age, 57 years; IQR, 20 years], 36 male participants; validation data set: 10 participants [mean age, 44 years; IQR, 17 years], seven male participants) were included. The sensitivity and specificity of rAMIRA for ALS were 60% (23 of 38) and 97% (91 of 94) in the study data set and 100% (10 of 10) and 93% (14 of 15) in the validation data set, respectively. Histopathologic analysis showed distinct loss of myelinated axons in the localization of the hyperintensities observed at rAMIRA imaging performed in situ and after organ extraction. Conclusion The recently defined marker at rAMIRA MRI may be a promising tool for assessing upper motor neuron degeneration in the lateral CST in patients with ALS. Clinical trials registration no. NCT03561623, NCT05764434, NCT06137612 © RSNA, 2024 Supplemental material is available for this article.

Background: Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration., Objectives: To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF., Methods: Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8-45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP)., Results: MP perfusion score and QDP correlated strongly with the CE perfusion score (both r  = 0.81; p  < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 ( r  = -0.75 and r  = -0.83; p  < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated ( r  = 0.74 and r  = 0.78; both p  < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated ( r  = 0.88 and r  = 0.86; both p  < 0.01)., Conclusion: MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials., Competing Interests: MS reports research grants from the German Federal Ministry of Education and Research (BMBF), the German Research Foundation (DFG) and Vertex Pharmaceuticals paid to the institution; personal fees for participation in advisory boards or consulting from Vertex Pharmaceuticals. MW reports research grants from Vertex Pharmaceuticals paid to the institution; consulting fees from Boehringer Ingelheim and Vertex Pharmaceuticals paid to the institution; lecture fees from Vertex Pharmaceuticals paid to the institution. MM reports research grants from the German Federal Ministry of Education and Research (BMBF), the German Research Foundation (DFG) and Vertex Pharmaceuticals paid to the institution; personal fees for participation in advisory boards or consulting from Arrowhead Pharmaceuticals, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Vertex Pharmaceuticals; lecture fees from Vertex Pharmaceuticals; and travel reimbursement from Boehringer Ingelheim and Vertex Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Doellinger, Bauman, Roehmel, Stahl, Posch, Steffen, Pusterla, Bieri, Wielpütz and Mall.)

Purpose: To develop a novel signal representation for balanced steady state free precession (bSSFP) displaying its T 2 independence on B 1 and on magnetization transfer (MT) effects., Methods: A signal model for bSSFP is developed that shows only an explicit dependence (up to a scaling factor) on E 2 (and, therefore, T 2 ) and a novel parameter c (with implicit dependence on the flip angle and E 1 ). Moreover, it is shown that MT effects, entering the bSSFP signal via a binary spin bath model, can be captured by a redefinition of T 1 and, therefore, leading to modification of E 1 , resulting in the same signal model. Various sets of phase-cycled bSSFP brain scans (different flip angles, different TR, different RF pulse durations, and different number of phase cycles) were recorded at 3 T. The parameters T 2 (E 2 ) and c were estimated using a variable projection (VARPRO) method and Monte-Carlo simulations were performed to assess T 2 estimation precision., Results: Initial experiments confirmed the expected independence of T 2 on various protocol settings, such as TR, the flip angle, B 1 field inhomogeneity, and the RF pulse duration. Any variation (within the explored range) appears to directly affect the estimation of the parameter c only-in agreement with theory., Conclusion: BSSFP theory predicts an extraordinary feature that all MT and B 1 -related variational aspects do not enter T 2 estimation, making it a potentially robust methodology for T 2 quantification, pending validation against existing standards., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background and Purpose: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator-independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA-derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS., Methods: A total of 36 patients with ALS (mean [SD] age 61.7 [12.6] years, 14 women) and 36 healthy, age- and sex-matched controls (HCs; mean [SD] age 63.1 [12.1] years, 14 women) underwent two-dimensional axial rAMIRA imaging at the inter-vertebral disc levels C2/3-C5/C6 and the lumbar enlargement level T max . ALS Functional Rating Scale-revised (ALSFRS-R) score, muscle strength, and sniff nasal inspiratory pressure (SNIP) were assessed., Results: Compared to HCs, GM and WM areas were reduced in patients at all cervical levels (p < 0.0001). GM area (p = 0.0001), but not WM area, was reduced at T max . Patients with King's Stage 3 showed significant GM atrophy at all levels, while patients with King's Stage 1 showed significant GM atrophy selectively at T max . SC GM area was significantly associated with muscle force at corresponding myotomes. GM area at C3/C4 was associated with ALSFRS-R (p < 0.001) and SNIP (p = 0.0016)., Conclusion: Patients with ALS assessed by rAMIRA imaging show significant cervical and thoracic SC GM and SC WM atrophy. SC GM area correlates with muscle strength and clinical disability. GM area reduction at T max may be an early disease sign. Longitudinal studies are warranted., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)