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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.

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.)

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.)

Objectives: In patients with congenital diaphragmatic hernia (CDH) the exact functional outcome of the affected lung side is still unknown, mainly due to the lack of spatially resolved diagnostic tools. Functional matrix-pencil decomposition (MP-) lung MRI fills this gap as it measures side-specific ventilation and perfusion. We aimed to assess the overall and side-specific pulmonary long-term outcomes of patients with CDH using lung function tests and MP-MRI., Methods: Thirteen school-aged children with CDH (seven with small and six with large defect-sized CDH, defined as > 50% of the chest wall circumference being devoid of diaphragm tissue) and thirteen healthy matched controls underwent spirometry, multiple-breath washout, and MP-MRI. The main outcomes were forced expiratory volume in 1 second (FEV 1 ), lung clearance index (LCI 2.5 ), ventilation defect percentage (VDP), and perfusion defect percentage (QDP)., Results: Patients with a large CDH showed significantly reduced overall lung function compared to healthy controls (mean difference [95%-CI adjusted ]: FEV 1 (z-score) -4.26 [-5.61, -2.92], FVC (z-score) -3.97 [-5.68, -2.26], LCI 2.5 (TO) 1.12 [0.47, 1.76], VDP (%) 8.59 [3.58, 13.60], QDP (%) 17.22 [13.16, 21.27]) and to patients with a small CDH. Side-specific examination by MP-MRI revealed particularly reduced ipsilateral ventilation and perfusion in patients with a large CDH (mean difference to contralateral side [95%-CI adjusted ]: VDP (%) 14.80 [10.50, 19.00], QDP (%) 23.50 [1.75, 45.20])., Conclusions: Data indicate impaired overall lung function with particular limitation of the ipsilateral side in patients with a large CDH. MP-MRI is a promising tool to provide valuable side-specific functional information in the follow-up of patients with CDH., Clinical Relevance Statement: In patients with congenital diaphragmatic hernia, easily applicable MP-MRI allows specific examination of the lung side affected by the hernia and provides valuable information on ventilation and perfusion with implications for clinical practice, making it a promising tool for routine follow-up., Key Points: • Functional matrix pencil decomposition (MP) MRI data from a small sample indicate reduced ipsilateral pulmonary ventilation and perfusion in children with large congenital diaphragmatic hernia (CDH). • Easily applicable pencil decomposition MRI provides valuable side-specific diagnostic information on lung ventilation and perfusion. This is a clear advantage over conventional lung function tests, helping to comprehensively follow up patients with congenital diaphragmatic hernia and monitor therapy effects., (© 2023. The Author(s).)

Purpose: The reproducibility of scientific reports is crucial to advancing human knowledge. This paper is a summary of our experience in replicating a balanced SSFP half-radial dual-echo imaging technique (bSTAR) using open-source frameworks as a response to the 2023 ISMRM "repeat it with me" Challenge., Methods: We replicated the bSTAR technique for thoracic imaging at 0.55T. The bSTAR pulse sequence is implemented in Pulseq, a vendor neutral open-source rapid sequence prototyping environment. Image reconstruction is performed with the open-source Berkeley Advanced Reconstruction Toolbox (BART). The replication of bSTAR, termed open-source bSTAR, is tested by replicating several figures from the published literature. Original bSTAR, using the pulse sequence and image reconstruction developed by the original authors, and open-source bSTAR, with pulse sequence and image reconstruction developed in this work, were performed in healthy volunteers., Results: Both echo images obtained from open-source bSTAR contain no visible artifacts and show identical spatial resolution and image quality to those in the published literature. A direct head-to-head comparison between open-source bSTAR and original bSTAR on a healthy volunteer indicates that open-source bSTAR provides adequate SNR, spatial resolution, level of artifacts, and conspicuity of pulmonary vessels comparable to original bSTAR., Conclusion: We have successfully replicated bSTAR lung imaging at 0.55T using two open-source frameworks. Full replication of a research method solely relying on information on a research paper is unfortunately rare in research, but our success gives greater confidence that a research methodology can be indeed replicated as described., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction: Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning., Methods: We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young ( N = 23; mean age = 23.39 years) and elderly ( N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI., Results: According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects., Discussion: In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging., Competing Interests: The 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 Schneider, Rajkovic, Krug, Caviezel, Reichert, Bieri, Schmidt, Borgwardt, Leyhe, Linnemann, Brühl, Lang and Melcher.)

Purpose: To investigate the prospects of a multigradient-echo (mGRE) acquisition for in vivo myelin water imaging at 0.55 T., Methods: Scans were performed on the brain of four healthy volunteers at 0.55 and 3 T, using a 3D mGRE sequence. The myelin water fraction (MWF) was calculated for both field strengths using a nonnegative least squares (NNLS) algorithm, implemented in the qMRLab suite. The quality of these maps as well as single-voxel fits were compared visually for 0.55 and 3 T., Results: The obtained MWF values at 0.55 T are consistent with previously reported ones at higher field strengths. The MWF maps are a considerable improvement over the ones at 3 T. Example fits show that 0.55 T data is better described by an exponential model than 3 T data, making the assumed multi-exponential model of the NNLS algorithm more accurate., Conclusion: This first assessment shows that mGRE myelin water imaging at 0.55 T is feasible and has the potential to yield better results than at higher fields., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objective: The potential of magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) for the detection and evolution of new multiple sclerosis (MS) lesions was analyzed., Methods: Nineteen patients with MS obtained conventional MRI, MTI, and DTI examinations bimonthly for 12 months and again after 24 months at 1.5 T MRI. MTI was acquired with balanced steady-state free precession (bSSFP) in 10 min (1.3 mm 3 isotropic resolution) yielding both magnetization transfer ratio (MTR) and quantitative magnetization transfer (qMT) parameters (pool size ratio (F), exchange rate (kf), and relaxation times (T1/T2)). DTI provided fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)., Results: At the time of their appearance on MRI, the 21 newly detected MS lesions showed significantly reduced MTR/F/kf and prolonged T1/T2 parameters, as well as significantly reduced FA and increased AD/MD/RD. Significant differences were already observed for MTR 4 months and for qMT parameters 2 months prior to lesions' detection on MRI. DTI did not show any significant pre-lesional differences. Slightly reversed trends were observed for most lesions up to 8 months after their detection for qMT and less pronounced for MTR and three diffusion parameters, while appearing unchanged on MRI., Conclusions: MTI provides more information than DTI in MS lesions and detects tissue changes 2 to 4 months prior to their appearance on MRI. After lesions' detection, qMT parameter changes promise to be more sensitive than MTR for the lesions' evolutional assessment. Overall, bSSFP-based MTI adumbrates to be more sensitive than MRI and DTI for the early detection and follow-up assessment of MS lesions., Clinical Relevance Statement: When additionally acquired in routine MRI, fast bSSFP-based MTI can complement the MRI/DTI longitudinal lesion assessment by detecting MS lesions 2-4 months earlier than with MRI, which could implicate earlier clinical decisions and better follow-up/treatment assessment in MS patients., Key Points: • Magnetization transfer imaging provides more information than DTI in multiple sclerosis lesions and can detect tissue changes 2 to 4 months prior to their appearance on MRI. • After lesions' detection, quantitative magnetization transfer changes are more pronounced than magnetization transfer ratio changes and therefore promise to be more sensitive for the lesions' evolutional assessment. • Balanced steady-state free precession-based magnetization transfer imaging is more sensitive than MRI and DTI for the early detection and follow-up assessment of multiple sclerosis lesions., (© 2023. The Author(s).)

Purpose: To improve the gray/white matter contrast of magnetization prepared rapid gradient echo (MP-RAGE) MRI at 0.55 T by optimizing the acquisition and sequence kernel parameters., Methods: A segmented magnetization prepared rapid gradient echo prototype sequence was implemented with (MP-RAGE*) and without (MP-FISP*) radiofrequency spoiling. Optimized parameters were derived with the assistance of an extended phase graph signal simulation as a function of the relaxation times, the flip angle, the delay times, and the effective inversion time using segmentation. The resulting protocols were compared to the MP-RAGE product sequence offered by the vendor in terms of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). A tissue segmentation reproducibility study was performed on three volunteers for the product MP-RAGE and the MP-FISP*., Results: The MP-RAGE simulation reproduced the parameters already used in the product MP-RAGE on the scanner. An average CNR improvement of 15% for the custom MP-RAGE* over the product MP-RAGE and additional 22% for the MP-FISP* over the MP-RAGE* were observed, which is in accordance with the simulation results. The total improvement, averaged over all volunteers and regions, was 41%. The reproducibility study did not yield a significant difference between MP-RAGE and MP-FISP*., Conclusion: We presented some easy-to-implement adjustments to the MP-RAGE sequence at 0.55 T, which can lead to an overall average improvement of 41% in CNR., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To implement cine phase-contrast balanced SSFP (PC-bSSFP) for low-field 0.55T cardiac MRI by exploiting the intrinsic flow sensitivity of the bSSFP slice-select gradient and the in-plane phase-cancelation properties of radial trajectories, enabling self-gated and referenceless PC-bSSFP flow quantification at 0.55 T., Methods: A free-running, tiny golden-angle radial PC-bSSFP approach was implemented on 0.55T and 1.5T systems. Cardiac and respiratory self-gating was incorporated to enable electrocardiogram-free scanning during breath-hold and free-breathing. By exploiting the intrinsic in-plane phase-cancelation properties of radial acquisitions and background phase fitting, referenceless single-point PC-bSSFP was realized. In vivo data were acquired in the ascending aorta of healthy subjects at 0.55 T and 1.5 T during breath-hold and free-breathing. Flow data, SNR, and velocity-to-noise ratio were compared relative to data obtained with phase-contrast spoiled gradient-echo variants., Results: Velocities acquired with PC-bSSFP compared well with data from phase-contrast spoiled gradient-echo (RMSE v  = 5.8 cm/s). PC-bSSFP at 0.55 T resulted in high-quality cine magnitude images and phase maps with sufficient SNR and velocity-to-noise ratio. Breath-hold and free-breathing PC-bSSFP performed very similarly, with comparable flow quantification (RMSE v  = 5.7 cm/s). Referenceless single-point PC-bSSFP results agreed well with two-point PC-bSSFP (-1.8 ± 5.2 cm/s) while reducing scan times 2-fold., Conclusion: PC-bSSFP is feasible on low-field 0.55T systems, producing high-quality cine images while permitting simultaneous aortic flow measurements during breath-hold and free-breathing and without the need for electrocardiogram gating., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction: Previous studies in humans and rats suggest that erythritol might positively affect vascular function, xylitol decrease visceral fat mass and both substances improve glycaemic control. The objective of this study was to investigate the impact of a 5-week intake of erythritol and xylitol on vascular function, abdominal fat and blood lipids, glucose tolerance, uric acid, hepatic enzymes, creatinine, gastrointestinal tolerance and dietary patterns in humans with obesity., Methods: Forty-two participants were randomised to consume either 36 g erythritol, 24 g xylitol, or no substance daily for 5 weeks. Before and after the intervention, arterial stiffness (pulse wave velocity, arteriolar-to-venular diameter ratio), abdominal fat (liver volume, liver fat percentage, visceral and subcutaneous adipose tissue, blood lipids), glucose tolerance (glucose and insulin concentrations), uric acid, hepatic enzymes, creatinine, gastrointestinal tolerance and dietary patterns were assessed. Data were analysed by linear mixed effect model., Results: The 5-week intake of erythritol and xylitol showed no statistically significant effect on vascular function. Neither the time nor the treatment effects were significantly different for pulse wave velocity (time effect: p=0.079, Cohen's D (95% CI) -0.14 (-0.54-0.25); treatment effect: p=0.792, Cohen's D (95% CI) control versus xylitol: -0.11 (-0.61-0.35), control versus erythritol: 0.05 (0.44-0.54), erythritol versus xylitol: 0.07 (-0.41-0.54)). There was no statistically significant effect on abdominal fat, glucose tolerance, uric acid, hepatic enzymes and creatinine. Gastrointestinal tolerance was good except for a few diarrhoea-related symptoms. Participants of all groups reduced their consumption of sweetened beverages and sweets compared with preintervention., Conclusions: The 5-week intake of erythritol and xylitol showed no statistically significant effects on vascular function, abdominal fat, or glucose tolerance in people with obesity., Clinical Trial Registration: NCT02821923., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To demonstrate the feasibility of high-resolution morphologic lung MRI at 0.55 T using a free-breathing balanced steady-state free precession half-radial dual-echo imaging technique (bSTAR)., Methods: Self-gated free-breathing bSTAR (TE 1 /TE 2 /TR of 0.13/1.93/2.14 ms) lung imaging in five healthy volunteers and a patient with granulomatous lung disease was performed using a 0.55 T MR-scanner. A wobbling Archimedean spiral pole (WASP) trajectory was used to ensure a homogenous coverage of k-space over multiple breathing cycles. WASP uses short-duration interleaves randomly tilted by a small polar angle and rotated by a golden angle about the polar axis. Data were acquired continuously over 12:50 min. Respiratory-resolved images were reconstructed off-line using compressed sensing and retrospective self-gating. Reconstructions were performed with a nominal resolution of 0.9 mm and a reduced isotropic resolution of 1.75 mm corresponding to shorter simulated scan times of 8:34 and 4:17 min, respectively. Analysis of apparent SNR was performed in all volunteers and reconstruction settings., Results: The technique provided artifact-free morphologic lung images in all subjects. The short TR of bSTAR in conjunction with a field strength of 0.55 T resulted in a complete mitigation of off-resonance artifacts in the chest. Mean SNR values in healthy lung parenchyma for the 12:50 min scan were 3.6 ± 0.8 and 24.9 ± 6.2 for 0.9 mm and 1.75 mm reconstructions, respectively., Conclusion: This study demonstrates the feasibility of morphologic lung MRI with a submillimeter isotropic spatial resolution in human subjects with bSTAR at 0.55 T., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicates that GCs may negatively impact brown adipose tissue (BAT) activity in rodents and humans., Methods: We performed a randomised, double-blinded cross-over trial in 16 healthy men (clinicaltrials.govNCT03269747). Participants received 40 mg of prednisone per day for one week or placebo. After a washout period of four weeks, participants crossed-over to the other treatment arm. Primary endpoint was the increase in resting energy expenditure (EE) in response to a mild-cold stimulus (cold-induced thermogenesis, CIT). Secondary outcomes comprised mean 18 F-FDG uptake into supraclavicular BAT (SUV mean ) as determined by FDG-PET/CT, volume of the BAT depot as well as fat content determined by MRI. The plasma metabolome and the transcriptome of supraclavicular BAT and of skeletal muscle biopsies after each treatment period were analysed., Findings: Sixteen participants were recruited to the trial and completed it successfully per protocol. After prednisone treatment resting EE was higher both during warm and cold conditions. However, CIT was similar, 153 kcal/24 h (95% CI 40-266 kcal/24 h) after placebo and 186 kcal/24 h (95% CI 94-277 kcal/24 h, p = 0.38) after prednisone. SUV mean of BAT after cold exposure was not significantly affected by prednisone (3.36 g/ml, 95% CI 2.69-4.02 g/ml, vs 3.07 g/ml, 95% CI 2.52-3.62 g/ml, p = 0.28). Results of plasma metabolomics and BAT transcriptomics corroborated these findings. RNA sequencing of muscle biopsies revealed higher expression of genes involved in calcium cycling. No serious adverse events were reported and adverse events were evenly distributed between the two treatments., Interpretation: Prednisone increased EE in healthy men possibly by altering skeletal muscle calcium cycling. Cold-induced BAT activity was not affected by GC treatment, which indicates that the unfavourable metabolic effects of GCs are independent from thermogenic adipocytes., Funding: Grants from Swiss National Science Foundation (PZ00P3&#95;167823), Bangerter-Rhyner Foundation and from Nora van der Meeuwen-Häfliger Foundation to MJB. A fellowship-grant from the Swiss National Science Foundation (SNF211053) to WS. Grants from German Research Foundation (project number: 314061271-TRR 205) and Else Kröner-Fresenius (grant support 2012&#95;A103 and 2015&#95;A228) to MR., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: With improvement in supportive therapies and the introduction of cystic fibrosis transmembrane conductance regulator (CFTR)-modulator treatment in patients with cystic fibrosis (CF), milder disease courses are expected. Therefore, sensitive parameters are needed to monitor disease course and effects of CFTR-modulators. Functional lung MRI using matrix-pencil decomposition (MP-MRI) is a promising tool for assessing ventilation and perfusion quantitatively. This study aimed to assess the treatment effect of elexacaftor/tezacaftor/ivacaftor combination regimen (ELX/TEZ/IVA) on measures of structural and functional lung abnormalities., Methods: 24 children with CF underwent lung function tests (multiple breath washout, spirometry), functional and structural MRI twice (one year apart) before and once after at least two weeks (mean 4.7 ± 2.6 months) on ELX/TEZ/IVA. Main outcomes were changes (Δ) upon ELX/TEZ/IVA in lung function, defect percentage of ventilation (VDP) and perfusion (QDP), defect distribution index of ventilation and perfusion (DDI V, DDI Q ), and Eichinger score. Statistical analyses were performed using paired t-tests and multilevel regression models with bootstrapping., Results: We observed a significant improvement in lung function, structural and functional MRI parameters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ΔLCI 2.5 (TO) -0.84 (-1.62 to -0.06); ΔFEV 1 (z-score) 1.05 (0.56 to 1.55); ΔVDP (% of impairment) -6.00 (-8.44 to -3.55); ΔQDP (% of impairment) -3.90 (-5.90 to -1.90); ΔDDI V -1.38 (-2.22 to -0.53); ΔDDI Q -0.31 (-0.73 to 0.12); ΔEichinger score -3.89 (-5.05 to -2.72)., Conclusions: Besides lung function tests, functional and structural MRI is a suitable tool to monitor treatment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in the future., (Copyright © 2022. Published by Elsevier B.V.)

Lung function testing and lung imaging are commonly used techniques to monitor respiratory diseases, such as cystic fibrosis (CF). The nitrogen (N 2 ) multiple-breath washout technique (MBW) has been shown to detect ventilation inhomogeneity in CF, but the underlying pathophysiological processes that are altered are often unclear. Dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) could potentially be performed simultaneously with MBW because both techniques require breathing of 100% oxygen (O 2 ) and may allow for visualisation of alterations underlying impaired MBW outcomes. However, simultaneous MBW and OE-MRI has never been assessed, potentially as it requires a magnetic resonance (MR) compatible MBW equipment. In this pilot study, we assessed whether MBW and OE-MRI can be performed simultaneously using a commercial MBW device that has been modified to be MR-compatible. We performed simultaneous measurements in five healthy volunteers aged 25-35 years. We obtained O 2 and N 2 concentrations from both techniques, and generated O 2 wash-in time constant and N 2 washout maps from OE-MRI data. We obtained good quality simultaneous measurements in two healthy volunteers due to technical challenges related to the MBW equipment and poor tolerance. Oxygen and N 2 concentrations from both techniques, as well as O 2 wash-in time constant maps and N 2 washout maps could be obtained, suggesting that simultaneous measurements may have the potential to allow for comparison and visualization of regional differences in ventilation underlying impaired MBW outcomes. Simultaneous MBW and OE-MRI measurements can be performed with a modified MBW device and may help to understand MBW outcomes, but the measurements are challenging and have poor feasibility., Competing Interests: Conflict of interest statement Eco Medics AG (Duernten, Switzerland) produced the customized MBW setup and a research version of their commercial software Spiroware 3.3. A.C. Kentgens is recipient of a Swiss Government Excellence Scholarship from the Swiss Confederation, Federal Department of Economic Affairs, Education and Research (EAER). F. Santini reports research grants from the Swiss National Science Foundation and consulting fees of Hoffmann – La Roche paid to the institution. P. Latzin reports grants from Vertex and OM Pharma paid to the institution; personal payments or honoraria from Vertex, Vifor and OM Pharma; payments or honoraria from Vertex, Vifor and OM Pharma paid to the institution; personal fees for participation on a Data Safety Monitoring Board or Advisory Board from Polyphor, Santhera (DMC), Vertex, OM pharma, Vifor and Sanofi Aventis; and fees for participation on a Data Safety Monitoring Board or Advisory Board from Polyphor, Vertex, OM pharma and Vifor paid to the institution, all outside the submitted work. K.A. Ramsey reports a grant from Vertex paid to the institution. Otherwise, all other authors report no other competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Spinal cord (SC) gray and white matter pathology plays a central role in multiple sclerosis (MS)., Objective: We aimed to investigate the extent, pattern, and clinical relevance of SC gray and white matter atrophy in vivo., Methods: 39 relapsing-remitting patients (RRMS), 40 progressive MS patients (PMS), and 24 healthy controls (HC) were imaged at 3T using the averaged magnetization inversion recovery acquisitions sequence. Total and lesional cervical gray and white matter, and posterior (SCPH) and anterior horn (SCAH) areas were automatically quantified. Clinical assessment included the expanded disability status scale, timed 25-foot walk test, nine-hole peg test, and the 12-item MS walking scale., Results: PMS patients had significantly reduced cervical SCAH - but not SCPH - areas compared with HC and RRMS (both p  < 0.001). In RRMS and PMS, the cervical SCAH areas increased significantly less in the region of cervical SC enlargement compared with HC (all p  < 0.001). This reduction was more pronounced in PMS compared with RRMS (both p  < 0.001). In PMS, a lower cervical SCAH area was the most important magnetic resonance imaging (MRI)-variable for higher disability scores., Conclusion: MS patients show clinically relevant cervical SCAH atrophy, which is more pronounced in PMS and at the level of cervical SC enlargement.

Purpose: To demonstrate free-breathing thoracic MRI with a minimal-TR balanced steady-state free precession (bSSFP) technique using wobbling Archimedean spiral pole (WASP) trajectories., Methods: Phantom and free-breathing in vivo chest imaging in healthy volunteers was performed at 1.5T with a half-radial, dual-echo, bSSFP sequence, termed bSTAR. For maximum sampling efficiency, a single analog-to-digital converter window along the full bipolar readout was used. To ensure a homogeneous coverage of the k-space over multiple breathing cycles, radial k-space sampling followed short-duration Archimedean spiral interleaves that were randomly titled by a small polar angle and rotated by a golden angle about the polar axis; depticting a wobbling Archimedean spiral pole (WASP) trajectory. In phantom and in vivo experiments, WASP trajectories were compared to spiral phyllotaxis sampling in terms of eddy currents and were used to generate in vivo thorax images at different respiratory phases., Results: WASP trajectories provided artifact-free bSTAR imaging in both phantom and in vivo and respiratory self-gated reconstruction was successfully performed in all subjects. The amount of the acquired data allowed the reconstruction of 10 volumes at different respiratory levels with isotropic resolution of 1.77mm from a scan of 5.5minutes (using a TR of 1.32ms), and one high-resolution 1.16mm end-expiratory volume from a scan of 4.7minutes (using a TR of 1.42ms). The very short TR of bSTAR mitigated off-resonance artifacts despite the large field-of-view., Conclusion: We have demonstrated the feasibility of high-resolution free-breathing thoracic imaging with bSTAR using the wobbling Archimedean spiral pole in healthy subjects at 1.5T., (Copyright © 2022. Published by Elsevier GmbH.)

Purpose: To provide a robust whole-brain quantitative magnetization transfer (MT) imaging method that is not limited by long acquisition times., Methods: Two variants of a spiral 2D interleaved multi-slice spoiled gradient echo (SPGR) sequence are used for rapid quantitative MT imaging of the brain at 3 T. A dual flip angle, steady-state prepared, double-contrast method is used for combined B 1 and-T 1 mapping in combination with a single-contrast MT-prepared acquisition over a range of different saturation flip angles (50 deg to 850 deg) and offset frequencies (1 kHz and 10 kHz). Five sets (containing minimum 6 to maximum 18 scans) with different MT-weightings were acquired. In addition, main magnetic field inhomogeneities (ΔB 0 ) were measured from two Cartesian low-resolution 2D SPGR scans with different echo times. Quantitative MT model parameters were derived from all sets using a two-pool continuous-wave model analysis, yielding the pool-size ratio, F, their exchange rate, k f , and their transverse relaxation time, T 2r ., Results: Whole-brain quantitative MT imaging was feasible for all sets with total acquisition times ranging from 7:15 min down to 3:15 min. For accurate modeling, B 1 -correction was essential for all investigated sets, whereas ΔB 0 -correction showed limited bias for the observed maximum off-resonances at 3 T., Conclusion: The combination of rapid B 1 -T 1 mapping and MT-weighted imaging using a 2D multi-slice spiral SPGR research sequence offers excellent prospects for rapid whole-brain quantitative MT imaging in the clinical setting., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: One of the authors, Josef Pfeuffer, is employed by Siemens Healthineers., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: Although cervical spinal cord (cSC) area is an established biomarker in MS, there is currently a lack of longitudinal assessments of cSC gray and white matter areas., Objective: We conducted an explorative analysis of longitudinal changes of cSC gray and white matter areas in MS patients., Methods: 65 MS patients (33 relapsing-remitting; 20 secondary progressive and 12 primary progressive) and 20 healthy controls (HC) received clinical and upper cSC MRI assessments over 1.10±0.28 years. cSC compartments were quantified on MRI using the novel averaged magnetization inversion recovery acquisitions sequence (in-plane resolution=0.67 × 0.67mm 2 ), and in-house developed post-processing methods. Patients were stratified regarding clinical progression., Results: Patients with clinical progression showed faster reduction of cSC areas over time at the level of cSC enlargement (approximate vertebral level C4-C5) compared to stable patients (p<0.05). In addition, when compared to the rostral-cSC (approximate vertebral level C2-C3), a preferential reduction of cSC and white matter areas over time at the level of cSC enlargement (p<0.05 and p<0.01, respectively) was demonstrated only in patients with clinical progression, but not in stable MS patients and HC. Compared to HC, MS patients showed comparable changes over time in all cSC compartments., Conclusions: MS patients with clinical disease progression demonstrate subtle signs of a more pronounced tissue loss at the level of cSC enlargement. Future studies should consider larger sample sizes and more extended observation periods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background and Purpose: Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal cord compartment segmentation (SCORE) in patients with MS., Materials and Methods: The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer., Results: The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all P  < .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas ( P  < .05), and total anterior horn areas ( P  < .01 respectively), as measured with SCORE., Conclusions: We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers., (© 2023 by American Journal of Neuroradiology.)

Background: T 2 * anisotropy affects the clinical assessment of tendons (magic-angle artifact) and may be a source of T 2 *-misinterpretation., Purpose: To analyze T 2 *-anisotropy and T 2 *-decay of Achilles and patellar tendons in vitro at microscopic resolution using a variable-echo-time (vTE) sequence., Study Type: Prospective., Specimen: Four human Achilles and four patellar tendons., Field Strength/sequence: A 7 T MR-microscopy; 3D-vTE spoiled-gradient-echo-sequence (T 2 *-mapping)., Assessment: All tendons were measured at 0° and 55° relative to B 0 . Additional angles were measured for one Achilles and one patellar tendon for a total of 11 angles ranging from 0° to 90°. T 2 *-decay was analyzed with mono- and bi-exponential signal fitting. Mono-exponential T 2 *-values (T 2 * m ), short and long T 2 *-components (T 2 * s , T 2 * l ), and the fraction of the short component F s of the bi-exponential T 2 *-fit were calculated. T 2 *-decay characteristics were compared with morphological MRI and histologic findings based on a region-of-interest analysis., Statistical Tests: Akaike information criterion (AIC C ), F-test, and paired t-test. A P value smaller than the α-level of 0.05 was considered statistically significant., Results: T 2 * m -values between fiber-to-field angles of 0° and 55° were increased on average from T 2 * m (0°) = 1.92 msec to T 2 * m (55°) = 29.86 msec (15.5-fold) in the Achilles and T 2 * m (0°) = 1.46 msec to T 2 * m (55°) = 23.33 msec (16.0-fold) in the patellar tendons. The changes in T 2 * m -values were statistically significant. For the whole tendon, according to F-test and AIC C , a bi-exponential model was preferred for angles close to 0°, while the mono-exponential model tended to be preferred at angles close to 55°., Conclusion: MR-microscopy provides a deeper insight into the relationship between T 2 *-decay (mono- vs. bi-exponential model) and tendon heterogeneity. Changes in fiber-to-field angle result in significant changes in T 2 *-values. Thus, we conclude that awareness of T 2 *-anisotropy should be noted in quantitative T 2 *-mapping of tendons to avoid T 2 *-misinterpretation such as a false positive detection of degeneration due to large fiber-to-field angles., Evidence Level: 2 TECHNICAL EFFICACY: Stage 2., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To introduce a widely applicable workflow for pulmonary lobe segmentation of MR images using a recurrent neural network (RNN) trained with chest CT datasets. The feasibility is demonstrated for 2D coronal ultrafast balanced SSFP (ufSSFP) MRI., Methods: Lung lobes of 250 publicly accessible CT datasets of adults were segmented with an open-source CT-specific algorithm. To match 2D ufSSFP MRI data of pediatric patients, both CT data and segmentations were translated into pseudo-MR images that were masked to suppress anatomy outside the lung. Network-1 was trained with pseudo-MR images and lobe segmentations and then applied to 1000 masked ufSSFP images to predict lobe segmentations. These outputs were directly used as targets to train Network-2 and Network-3 with non-masked ufSSFP data as inputs, as well as an additional whole-lung mask as input for Network-2. Network predictions were compared to reference manual lobe segmentations of ufSSFP data in 20 pediatric cystic fibrosis patients. Manual lobe segmentations were performed by splitting available whole-lung segmentations into lobes., Results: Network-1 was able to segment the lobes of ufSSFP images, and Network-2 and Network-3 further increased segmentation accuracy and robustness. The average all-lobe Dice similarity coefficients were 95.0 ± 2.8 (mean ± pooled SD [%]) and 96.4 ± 2.5, 93.0 ± 2.0; and the average median Hausdorff distances were 6.1 ± 0.9 (mean ± SD [mm]), 5.3 ± 1.1, 7.1 ± 1.3 for Network-1, Network-2, and Network-3, respectively., Conclusion: Recurrent neural network lung lobe segmentation of 2D ufSSFP imaging is feasible, in good agreement with manual segmentations. The proposed workflow might provide access to automated lobe segmentations for various lung MRI examinations and quantitative analyses., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background Evidence regarding short-term effects of electronic nicotine delivery systems (ENDS) and tobacco smoke on lung ventilation and perfusion is limited. Purpose To examine the immediate effect of ENDS exposure and tobacco smoke on lung ventilation and perfusion by functional MRI and lung function tests. Materials and Methods This prospective observational pilot study was conducted from November 2019 to September 2021 (substudy of randomized controlled trial NCT03589989). Included were 44 healthy adult participants (10 control participants, nine former tobacco smokers, 13 ENDS users, and 12 active tobacco smokers; mean age, 41 years ± 12 [SD]; 28 men) who underwent noncontrast-enhanced matrix pencil MRI and lung function tests before and immediately after the exposure to ENDS products or tobacco smoke. Baseline measurements were acquired after 2 hours of substance abstinence. Postexposure measurements were performed immediately after the exposure. MRI showed semiquantitative measured impairment of lung perfusion (R Q ) and fractional ventilation (R FV ) impairment as percentages of affected lung volume. Lung clearance index (LCI) was assessed by nitrogen multiple-breath washout to capture ventilation inhomogeneity and spirometry to assess airflow limitation. Absolute differences were calculated with paired Wilcoxon signed-rank test and differences between groups with unpaired Mann-Whitney test. Healthy control participants underwent two consecutive MRI measurements to assess MRI reproducibility. Results MRI was performed and lung function measurement was acquired in tobacco smokers and ENDS users before and after exposure. MRI showed a decrease of perfusion after exposure (R Q , 8.6% [IQR, 7.2%-10.0%] to 9.1% [IQR, 7.8%-10.7%]; P = .03) and no systematic change in R FV ( P = .31) among tobacco smokers. Perfusion increased in participants who used ENDS after exposure (R Q , 9.7% [IQR, 7.1%-10.9%] to 9.0% [IQR, 6.9%-10.0%]; P = .01). R FV did not change ( P = .38). Only in tobacco smokers was LCI elevated after smoking ( P = .02). Spirometry indexes did not change in any participants. Conclusion MRI showed a decrease of lung perfusion after exposure to tobacco smoke and an increase of lung perfusion after use of electronic nicotine delivery systems. © RSNA, 2022 Online supplemental material is available for this article . See also the editorial by Kligerman in this issue.

Objective: To determine if patients with post-polio syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient-reported functional decline., Methods: Twenty patients diagnosed with PPS (March of Dimes criteria) and 20 age- and sex-matched healthy controls (HC) underwent 3T axial 2D-rAMIRA magnetic resonance imaging at the intervertebral disc levels C2/C3-C6/C7, T9/T10 and the lumbar enlargement level (T max ) (0.5 × 0.5 mm 2 in-plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self-reported fatigue, depression and pain measures were assessed., Results: Post-polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p = 0.001), C4/C5 (p < 0.001), C5/C6 (p = 0.004) and T max (p = 0.041) compared to HC. SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain and depression. SCGM area Tmax together with age and sex explained 68% of ankle dorsiflexion strength variance. No associations were found with age at or time since infection. Patients reporting PPS-related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity., Conclusions: Patients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS-related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Purpose: Respiratory motion is one of the major challenges in radiotherapy. In this work, a comprehensive and clinically plausible set of 4D numerical phantoms, together with their corresponding "ground truths," have been developed and validated for 4D radiotherapy applications., Methods: The phantoms are based on CTs providing density information and motion from multi-breathing-cycle 4D Magnetic Resonance imagings (MRIs). Deformable image registration (DIR) has been utilized to extract motion fields from 4DMRIs and to establish inter-subject correspondence by registering binary lung masks between Computer Tomography (CT) and MRI. The established correspondence is then used to warp the CT according to the 4DMRI motion. The resulting synthetic 4DCTs are called 4DCT(MRI)s. Validation of the 4DCT(MRI) workflow was conducted by directly comparing conventional 4DCTs to derived synthetic 4D images using the motion of the 4DCTs themselves (referred to as 4DCT(CT)s). Digitally reconstructed radiographs (DRRs) as well as 4D pencil beam scanned (PBS) proton dose calculations were used for validation., Results: Based on the CT image appearance of 13 lung cancer patients and deformable motion of five volunteer 4DMRIs, synthetic 4DCT(MRI)s with a total of 871 different breathing cycles have been generated. The 4DCT(MRI)s exhibit an average superior-inferior tumor motion amplitude of 7 ± 5 mm (min: 0.5 mm, max: 22.7 mm). The relative change of the DRR image intensities of the conventional 4DCTs and the corresponding synthetic 4DCT(CT)s inside the body is smaller than 5% for at least 81% of the pixels for all studied cases. Comparison of 4D dose distributions calculated on 4DCTs and the synthetic 4DCT(CT)s using the same motion achieved similar dose distributions with an average 2%/2 mm gamma pass rate of 90.8% (min: 77.8%, max: 97.2%)., Conclusion: We developed a series of numerical 4D lung phantoms based on real imaging and motion data, which give realistic representations of both anatomy and motion scenarios and the accessible "ground truth" deformation vector fields of each 4DCT(MRI). The open-source code and motion data allow foreseen users to generate further 4D data by themselves. These numeric 4D phantoms can be used for the development of new 4D treatment strategies, 4D dose calculations, DIR algorithm validations, as well as simulations of motion mitigation and different online image guidance techniques for both proton and photon radiation therapy., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: To show that for tissues the conspicuous asymmetries in the frequency response function of bSSFP can be mitigated by using a short enough TR., Theory and Methods: Configuration theory indicates that bSSFP becomes apparently "pure" (i.e., exhibiting a symmetric profile) in the limit of TR → 0 . To this end, the frequency profile of bSSFP was measured as a function of the TR using a manganese-doped aqueous probe, as well as brain tissue that was shown to exhibit a pronounced asymmetry due to its microstructure. The frequency response function was sampled using N = 72 (phantom) and N = 36 (in vivo) equally distributed linear RF phase increments in the interval [ 0 , 2 π ) . Imaging was performed with 2.0 mm isotropic resolution over a TR range of 1.5-8 ms at 3 and 1.5 T., Results: As expected, pure substances showed a symmetric TR-independent frequency profile, whereas brain tissue revealed a pronounced asymmetry. The observed asymmetry for the tissue, however, decreases with decreasing TR and gives strong evidence that the frequency response function of bSSFP becomes symmetric in the limit of TR → 0 , in agreement with theory. The limit of apparently pure bSSFP imaging can thus be achieved for a TR ∼ 1.5 ms at 1.5 T, whereas at 3 T, tissues still show some residual asymmetry., Conclusion: In the limit of short enough TR, tissues become apparently pure for bSSFP. This limit can be reached for brain tissue at 1.5 T with TR ∼ 1-2 ms at clinically relevant resolutions., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To present a new complex-valued B 1 + mapping method for electrical properties tomography using Carr-Purcell spin echoes., Methods: A Carr-Purcell (CP) echo train generates pronounced flip-angle dependent oscillations that can be used to estimate the magnitude of B 1 + . To this end, a dictionary is used that takes into account the slice profile as well as T 2 relaxation along the echo train. For validation, the retrieved B 1 + map is compared with the actual flip angle imaging (AFI) method in a phantom (79 ε 0 , 0.34 S/m). Moreover, the phase of the first echo reflects the transceive phase. Overall, the CP echo train yields an estimate of the complex-valued B 1 + , allowing electrical properties tomography with both permittivity and conductivity. The presented method is evaluated in phantom scans as well as for in vivo brain at 3 T., Results: In the phantom, the obtained magnitude B 1 + maps retrieved from the CP echo train and the AFI method show excellent agreement, and both the reconstructed estimated permittivity (79 ± 3) ε 0 and conductivity (0.35 ± 0.04) S/m values are in accordance with expectations. In the brain, the obtained electrical properties are also close to expectations. In addition to the retrieved complex B 1 + information, the decay of the CP echo trains also yields an estimate for T 2 ., Conclusion: The CP sequence can be used to simultaneously provide both B 1 + magnitude and phase estimations, and therefore allows for full reconstruction of the electrical properties., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background and Purpose: Radiation necrosis, for which abnormal WM enhancement is a hallmark, is an uncommon complication of craniospinal irradiation in children with medulloblastoma. The magnetization transfer ratio measures macromolecular content, dominated by myelin in the WM. We investigated whether the pretreatment supratentorial (nonsurgical) WM magnetization transfer ratio could predict patients at risk for radiation necrosis after radiation therapy for medulloblastoma., Materials and Methods: Ninety-five eligible patients with medulloblastoma (41% female; mean age, 11.0 [SD, 5.4]  years) had baseline balanced steady-state free precession MR imaging before proton or photon radiation therapy. Associations among baseline supratentorial magnetization transfer ratio, radiation necrosis (spontaneously resolving/improving parenchymal enhancement within the radiation field) 3 , age, and the presence of visible brain metastases were explored by logistic regression and parametric/nonparametric techniques as appropriate., Results: Twenty-three of 95 (24.2%) children (44% female; mean age, 10.7 [SD, 6.7] years) developed radiation necrosis after radiation therapy (19 infratentorial, 1 supratentorial, 3 both). The mean pretreatment supratentorial WM magnetization transfer ratio was significantly lower in these children (43.18 versus 43.50, P  = .03). There was no association between the supratentorial WM magnetization transfer ratio and age, sex, risk/treatment stratum, or the presence of visible brain metastases., Conclusions: A lower baseline supratentorial WM magnetization transfer ratio may indicate underlying structural WM susceptibility to radiation necrosis and may identify children at risk for developing radiation necrosis after craniospinal irradiation for medulloblastoma., (© 2022 by American Journal of Neuroradiology.)

Background: Inhalation therapy is one of the cornerstones of the daily treatment regimen in patients with cystic fibrosis (CF). Recommendations regarding the addition of bronchodilators, especially salbutamol are conflicting due to the lack of evidence. New diagnostic measures such as multiple-breath washout (MBW) and functional magnetic resonance imaging (MRI) have the potential to reveal new insights into bronchodilator effects in patients with CF., Objective: The objective of the study was to comprehensively assess the functional response to nebulized inhalation with salbutamol in children with CF., Methods: Thirty children aged 6-18 years with stable CF performed pulmonary function tests, MBW, and matrix pencil-MRI before and after standardized nebulized inhalation of salbutamol., Results: Lung clearance index decreased (improved) by -0.24 turnover (95% confidence interval [CI]: -0.53 to 0.06; p = 0.111). Percentage of the lung volume with impaired fractional ventilation and relative perfusion decreased (improved) by -0.79% (CI: -1.99 to 0.42; p = 0.194) and -1.31% (CI: -2.28 to -0.35; p = 0.009), respectively. Forced expiratory volume (FEV1) increased (improved) by 0.41 z-score (CI: 0.24-0.58; p < 0.0001). We could not identify specific clinical factors associated with a more pronounced effect of salbutamol., Conclusions: There is a positive short-term effect of bronchodilator inhalation on FEV1 in patients with CF, which is independent of ventilation inhomogeneity. Heterogeneous response between patients suggests that for prediction of a therapeutic effect this should be tested by spirometry in every patient individually., (© 2021 S. Karger AG, Basel.)

Purpose: Lung impairment from functional MRI is frequently assessed as defect percentage. The defect distribution, however, is currently not quantified. The purpose of this work was to develop a novel measure that quantifies how clustered or scattered defects in functional lung MRI appear, and to evaluate it in pediatric cystic fibrosis., Theory: The defect distribution index (DDI) calculates a score for each lung voxel categorized as defected. The index increases according to how densely and how far an expanding circle around a defect voxel contains more than 50% defect voxels., Methods: Fractional ventilation and perfusion maps of 53 children with cystic fibrosis were previously acquired with matrix pencil decomposition MRI. In this work, the DDI is compared to a visual score of 3 raters who evaluated how clustered the lung defects appear. Further, spearman correlations between DDI and lung function parameters were determined., Results: The DDI strongly correlates with the visual scoring (r = 0.90 for ventilation; r = 0.88 for perfusion; P < .0001). Although correlations between DDI and defect percentage are moderate to strong (r = 0.61 for ventilation; r = 0.75 for perfusion; P < .0001), the DDI distinguishes between patients with comparable defect percentage., Conclusion: The DDI is a novel measure for functional lung MRI. It provides complementary information to the defect percentage because the DDI assesses defect distribution rather than defect size. The DDI is applicable to matrix pencil MRI data of cystic fibrosis patients and shows very good agreement with human perception of defect distributions., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

This single-centered, randomized, double-blind, placebo-controlled study reports the results of L-Citrulline treatment for 24 weeks in patients with post-polio syndrome (PPS). Twenty-nine patients were randomized and assigned into receiving a treatment of 15 g L-Citrulline or placebo. The primary endpoint was the change of the 6 min walking distance test. Secondary endpoints included motor function measure, quantitative muscle strength, quantitative MRI and self-reported impairment questionnaires. Patients receiving L-Citrulline walked 17.5 longer in the 6 min walking distance test when compared to placebo group, however not statistically significant (95% CI = -14.69; 49.68, p = 0.298). None of the secondary endpoints showed a statistically significant change in the L-Citrulline group when compared to placebo group. The motor function measure showed a change of -0.78 (95% CI= [-3.39; 1.83] p = 0.563). Muscle degeneration of leg muscles assessed with quantitative MRI indicated no significant change (estimate= -0.01, 95% CI =-0.13; 0.11, p = 0.869). L-Citrulline was safe and well tolerated. In conclusion, administration of 15 g L-Citrulline daily for 24 weeks to patients with PPS showed no beneficial treatment effect in timed muscle function., Competing Interests: Declaration of Competing Interest DF is supported by the Thomi-Hopf-Foundation; the Neuromuscular Research Association Basel; the University of Basel Children's Hospital and the Department of Neurology, University Hospital Basel, Switzerland. He is the principle investigator for studies on spinal muscular atrophy sponsored by Hofmann-La Roche Ltd. The remaining authors declare that they have no competing interests., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to develop and validate an MRI protocol based on a variable echo time (vTE) sensitive to the short T2* components of the sciatic nerve., Materials and Methods: 15 healthy subjects (M/F: 9/6; age: 21-62) were scanned at 3T targeting the sciatic nerve at the thigh bilaterally, using a dual echo variable echo time (vTE) sequence (based on a spoiled gradient echo acquisition) with echo times of 0.98/5.37 ms. Apparent T2* (aT2*) values of the sciatic nerves were calculated with a mono-exponential fit and used for data comparison., Results: There were no significant differences in aT2* related to side, sex, age, and BMI, even though small differences for side were reported. Good-to-excellent repeatability and reproducibility were found for geometry of ROIs (Dice indices: intra-rater 0.68-0.7; inter-rater 0.70-0.72) and the related aT2* measures (intra-inter reader ICC 0.95-0.97; 0.66-0.85) from two different operators. Side-related signal-to-noise-ratio non-significant differences were reported, while contrast-to-noise-ratio measures were excellent both for side and echo., Discussion: Our study introduces a novel MR sequence sensitive to the short T2* components of the sciatic nerve and may be used for the study of peripheral nerve disorders.

Introduction: This proof-of-principle study aimed to demonstrate that magnetic resonance imaging (MRI) is sufficiently accurate for the detection of root canals using guided endodontics., Methods: One hundred extracted human teeth (anterior and premolar) were mounted onto 5 mandibular and 5 maxillary models, fitted with splints designed to accommodate a thin layer of aqueous gel for indirect imaging, and scanned by MRI. After MRI and intraoral scans were aligned using planning software, access cavities were planned virtually, and templates were manufactured with computer-aided design/computer-aided manufacturing, the access cavities were prepared. Cone-beam computed tomographic scans were performed and matched with the virtual preoperative planning data to determine the accuracy of access cavity preparation in terms of deviation between planned and prepared cavities in the mesiodistal and buccolingual dimensions and angle. Descriptive statistical analysis was performed, and the mean values were compared using the t test., Results: Ninety-one of 100 root canals were successfully scouted after MRI-guided access cavity preparation. The mean angle deviation was 1.82°. The mean deviation ranged from 0.21-0.31 mm at the base of the bur and from 0.28-0.44 mm at the tip of the bur. Preparation in the buccolingual dimension was significantly more precise in mandibular compared with maxillary teeth, and accuracy in the mesiodistal dimension was more precise in anterior teeth compared with premolars., Conclusions: This in vitro study demonstrated the suitability of MRI for guided endodontic access cavity preparation., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: Magnetization transfer ratio (MTR) histograms are used widely for the assessment of diffuse pathological changes in the brain. For broad clinical application, MTR scans should not only be fast, but confounding factors should also be minimized for high reproducibility. To this end, a 1-minute whole-brain spiral MTR method with intrinsic B 1 -field correction is introduced., Methods: A spiral multislice spoiled gradient-echo sequence with adaptable magnetization-transfer saturation pulses (angle β) is proposed. After a low-resolution single-shot spiral readout and a dummy preparation period, high-resolution images are acquired using an interleaved spiral readout. For whole-brain MTR imaging, 50 interleaved slices with three different magnetization-transfer contrasts (β = 0°, 350°, and 550°) together with an intrinsic B 1 -field map are recorded in 58.5 seconds on a clinical 3T system. From the three contrasts, two sets of MTR images are derived and used for subsequent B 1 correction, assuming a linear dependency on β. For validation, a binary spin bath model is used., Results: For the proposed B 1 -correction scheme, numerical simulations indicate for brain tissue a decrease of about a factor of 10 for the B 1 -related bias on MTR. As a result, following B 1 correction, MTR differences in gray and white matter become markedly accentuated, and the reproducibility of MTR histograms from scan-rescan experiments is improved. Furthermore, B 1 -corrected MTR histograms show a lower variability for age-matched normal-appearing brain tissue., Conclusion: From its speed and offering intrinsic B 1 correction, the proposed method shows excellent prospects for clinical studies that explore magnetization-transfer effects based on MTR histogram analysis., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: Muscles from patients with cerebral palsy (CP) are often spastic and form contractures that limit the range of motion. Injections of botulinum toxin A (BTX) into the calf muscles are an important treatment for functional equinus; however, improvement in gait function is not always achieved. BTX is also used to test muscle weakening for risk evaluation of muscle lengthening surgery. Our aim was to assess the effect of BTX over time on calf muscle properties in pediatric CP patients with MRI. Material and Methods: Six toe-walking CP patients (mean age 11.6 years) with indication for lengthening surgery were prospectively enrolled and received BTX injections into the gastrocnemius and soleus muscles. MRI scans at 3T of the lower legs and clinical examinations were performed pre-BTX, 6 weeks (6w), and 12 weeks (12w) post-BTX. A fat-suppressed 2D multi-spin-echo sequence was used to acquire T 2 maps and for segmentation. Fat fraction maps were calculated from 3D multi-echo Dixon images. Diffusion tensor imaging (DTI) with a 2D echo-planar imaging (EPI) sequence yielded maps of the mean apparent diffusion coefficient (ADC) and of the fractional anisotropy (FA). Hyperintense regions of interest (ROIs) on the T 2 -weighted (T 2 w) images at 6w were segmented in treated muscles. Mean values of T 2 , fat fraction, ADC, and FA were calculated in hyperintense ROIs and in reference ROIs in non-treated muscles. Results: Hyperintensity on T 2 w scans and increased T 2 (group mean ± standard deviation: 35 ± 1 ms pre-BTX, 45 ± 2 ms at 6w, and 44 ± 2 ms at 12w) were observed in all patients at the injection sites. The T 2 increase was spatially limited to parts of the injected muscles. FA increased (0.30 ± 0.03 pre-BTX, 0.34 ± 0.02 at 6w, and 0.36 ± 0.03 at 12w) while ADC did not change in hyperintense ROIs, indicating a BTX-induced increase in extracellular space and a simultaneous decrease of muscle fiber diameter. Fat fraction showed a trend for increase at 12w. Mean values in reference ROIs remained unchanged. Conclusion: MRI showed limited spatial distribution of the BTX-induced effects in pediatric CP patients. It could be a promising non-invasive tool for future studies to test BTX treatment protocols., Competing Interests: The 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., (Copyright © 2021 Weidensteiner, Madoerin, Deligianni, Haas, Bieri, Akinci D'Antonoli, Bracht-Schweizer, Romkes, De Pieri, Santini, Rutz, Brunner and Garcia.)

Purpose: To introduce phase-based conductivity mapping from a configuration space analysis., Methods: The frequency response function of balanced SSFP (bSSFP) is used to perform a configuration space analysis. It is shown that the transceive phase for conductivity mapping can be directly obtained by a simple fast Fourier transform of a series of phase-cycled bSSFP scans. For validation, transceive phase and off-resonance mapping with fast Fourier transform is compared with phase estimation using a recently proposed method, termed PLANET. Experiments were performed in phantoms and for in vivo brain imaging at 3 T using a quadrature head coil., Results: For fast Fourier transform, aliasing can lead to systematic phase errors. This bias, however, decreases rapidly with increasing sampling points. Interestingly, Monte Carlo simulations revealed a lower uncertainty for the transceive phase and the off-resonance using fast Fourier transform as compared with PLANET. Both methods, however, essentially retrieve the same phase information from a set of phase-cycled bSSFP scans. As a result, configuration-based conductivity mapping was successfully performed using eight phase-cycled bSSFP scans in the phantoms and for brain tissues. Overall, the retrieved values were in good agreement with expectations. Conductivity estimation and mapping of the field inhomogeneities can therefore be performed in conjunction with the estimation of other quantitative parameters, such as relaxation, using configuration theory., Conclusions: Phase-based conductivity mapping can be estimated directly from a simple Fourier analysis, such as in conjunction with relaxometry, using a series of phase-cycled bSSFP scans., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: MR imaging of the spinal cord (SC) gray matter (GM) at the cervical and lumbar enlargements' level may be particularly informative in lower motor neuron disorders, e. g., spinal muscular atrophy, but also in other neurodegenerative or autoimmune diseases affecting the SC. Radially sampled averaged magnetization inversion recovery acquisition (rAMIRA) is a novel approach to perform SC imaging in clinical settings with favorable contrast and is well-suited for SC GM quantitation. However, before applying rAMIRA in clinical studies, it is important to understand (i) the sources of inter-subject variability of total SC cross-sectional areas (TCA) and GM area (GMA) measurements in healthy subjects and (ii) their relation to age and sex to facilitate the detection of pathology-associated changes. In this study, we aimed to develop normalization strategies for rAMIRA-derived SC metrics using skull and spine-based metrics to reduce anatomical variability. Methods: Sixty-one healthy subjects (age range 11-93 years, 37.7% women) were investigated with axial two-dimensional rAMIRA imaging at 3T MRI. Cervical and thoracic levels including the level of the cervical (C4/C5) and lumbar enlargements (T max ) were examined. SC T2-weighted sagittal images and high-resolution 3D whole-brain T1-weighted images were acquired. TCA and GMAs were quantified. Anatomical variables with associations of | r | > 0.30 in univariate association with SC areas, and age and sex were used to construct normalization models using backward selection with TCA C4/C5 as outcome. The effect of the normalization was assessed by % relative standard deviation (RSD) reductions. Results: Mean inter-individual variability and the SD of the SC area metrics were considerable: TCA C4/5 : 8.1%/9.0; TCA Tmax : 8.9%/6.5; GMA C4/C5 : 8.6%/2.2; GMA Tmax : 12.2%/3.8. Normalization based on sex, brain WM volume, and spinal canal area resulted in RSD reductions of 23.7% for TCAs and 12.0% for GM areas at C4/C5. Normalizations based on the area of spinal canal alone resulted in RSD reductions of 10.2% for TCAs and 9.6% for GM areas at C4/C5, respectively. Discussion: Anatomic inter-individual variability of SC areas is substantial. This study identified effective normalization models for inter-subject variability reduction in TCA and SC GMA in healthy subjects based on rAMIRA imaging., Competing Interests: The 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., (Copyright © 2021 Kesenheimer, Wendebourg, Weigel, Weidensteiner, Haas, Richter, Sander, Horvath, Barakovic, Cattin, Granziera, Bieri and Schlaeger.)

Background: Cerebral palsy (CP) is the most common cause of physical disability in childhood. Muscle pathologies occur due to spasticity and contractures; therefore, diagnostic imaging to detect pathologies is often required. Imaging has been used to assess torsion or estimate muscle volume, but additional methods for characterizing muscle composition have not thoroughly been investigated. MRI fat fraction (FF) measurement can quantify muscle fat and is often a part of standard imaging in neuromuscular dystrophies. To date, FF has been used to quantify muscle fat and assess function in CP. In this study, we aimed to utilize a radiomics and FF analysis along with the combination of both methods to differentiate affected muscles from healthy ones. Materials and Methods: A total of 9 patients (age range 8-15 years) with CP and 12 healthy controls (age range 9-16 years) were prospectively enrolled (2018-2020) after ethics committee approval. Multi-echo Dixon acquisition of the calf muscles was used for FF calculation. The images of the second echo (TE = 2.87 ms) were used for feature extraction from the soleus, gastrocnemius medialis, and gastrocnemius lateralis muscles. The least absolute shrinkage and selection operator (LASSO) regression was employed for feature selection. RM, FF model (FFM), and combined model (CM) were built for each calf muscle. The receiver operating characteristic (ROC) curve and their respective area under the curve (AUC) values were used to evaluate model performance. Results: In total, the affected legs of 9 CP patients and the dominant legs of 12 healthy controls were analyzed. The performance of RM for soleus, gastrocnemius medialis, and gastrocnemius lateralis (AUC 0.92, 0.92, 0.82, respectively) was better than the FFM (AUC 0.88, 0.85, 0.69, respectively). The combination of both models always had a better performance than RM or FFM (AUC 0.95, 0.93, 0.83). FF was higher in the patient group (FF S 9.1%, FF GM 8.5%, and FF GL 10.2%) than control group (FF S 3.3%, FF GM 4.1%, FF GL 6.6%). Conclusion: The combination of MRI quantitative fat fraction analysis and texture analysis of muscles is a promising tool to evaluate muscle pathologies due to CP in a non-invasive manner., Competing Interests: The 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., (Copyright © 2021 Akinci D'Antonoli, Santini, Deligianni, Garcia Alzamora, Rutz, Bieri, Brunner and Weidensteiner.)

Imaging has become a valuable tool in the assessment of neuromuscular diseases, and, specifically, quantitative MR imaging provides robust biomarkers for the monitoring of disease progression. Quantitative evaluation of fat infiltration and quantification of the T2 values of the muscular tissue's water component (wT2) are two of the most essential indicators currently used. As each voxel of the image can contain both water and fat, a two-component model for the estimation of wT2 must be used. In this work, we present a fast method for reconstructing wT2 maps obtained from conventional multi-echo spin-echo (MESE) acquisitions and released as Free Open Source Software. The proposed software is capable of fast reconstruction thanks to extended phase graphs (EPG) simulations and dictionary matching implemented on a general-purpose graphic processing unit. The program can also perform more conventional biexponential least-squares fitting of the data and incorporate information from an external water-fat acquisition to increase the accuracy of the results. The method was applied to the scans of four healthy volunteers and five subjects suffering from facioscapulohumeral muscular dystrophy (FSHD). Conventional multi-slice MESE acquisitions were performed with 17 echoes, and additionally, a 6-echo multi-echo gradient-echo (MEGE) sequence was used for an independent fat fraction calculation. The proposed reconstruction software was applied on the full datasets, and additionally to reduced number of echoes, respectively, to 8, 5, and 3, using EPG and biexponential least-squares fitting, with and without incorporating information from the MEGE acquisition. The incorporation of external fat fraction maps increased the robustness of the fitting with a reduced number of echoes per datasets, whereas with unconstrained fitting, the total of 17 echoes was necessary to retain an independence of wT2 from the level of fat infiltration. In conclusion, the proposed software can successfully be used to calculate wT2 maps from conventional MESE acquisition, allowing the usage of an optimized protocol with similar precision and accuracy as a 17-echo acquisition. As it is freely released to the community, it can be used as a reference for more extensive cohort studies., Competing Interests: The 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., (Copyright © 2021 Santini, Deligianni, Paoletti, Solazzo, Weigel, de Sousa, Bieri, Monforte, Ricci, Tasca, Pichiecchio and Bergsland.)

Purpose: To investigate the repeatability and reproducibility of lung segmentation and their impact on the quantitative outcomes from functional pulmonary MRI. Additionally, to validate an artificial neural network (ANN) to accelerate whole-lung quantification., Method: Ten healthy children and 25 children with cystic fibrosis underwent matrix pencil decomposition MRI (MP-MRI). Impaired relative fractional ventilation (R FV ) and relative perfusion (R Q ) from MP-MRI were compared using whole-lung segmentation performed by a physician at two time-points (A t1 and A t2 ), by an MRI technician (B), and by an ANN (C). Repeatability and reproducibility were assess with Dice similarity coefficient (DSC), paired t-test and Intraclass-correlation coefficient (ICC)., Results: The repeatability within an observer (A t1 vs A t2 ) resulted in a DSC of 0.94 ± 0.01 (mean ± SD) and an unsystematic difference of -0.01% for R FV (P = .92) and +0.1% for R Q (P = .21). The reproducibility between human observers (A t1 vs B) resulted in a DSC of 0.88 ± 0.02, and a systematic absolute difference of -0.81% (P < .001) for R FV and -0.38% (P = .037) for R Q . The reproducibility between human and the ANN (A t1 vs C) resulted in a DSC of 0.89 ± 0.03 and a systematic absolute difference of -0.36% for R FV (P = .017) and -0.35% for R Q (P = .002). The ICC was >0.98 for all variables and comparisons., Conclusions: Despite high overall agreement, there were systematic differences in lung segmentation between observers. This needs to be considered for longitudinal studies and could be overcome by using an ANN, which performs as good as human observers and fully automatizes MP-MRI post-processing., (© 2020 International Society for Magnetic Resonance in Medicine.)

Pencil beam scanned (PBS) proton therapy of lung tumours is hampered by respiratory motion and the motion-induced density changes along the beam path. In this simulation study, we aim to investigate the effectiveness of proton beam tracking for lung tumours both under ideal conditions and in conjunction with a respiratory motion model guided by real-time ultrasound imaging of the liver. Multiple-breathing-cycle 4DMRIs of the thorax and abdominal 2D ultrasound images were acquired simultaneously for five volunteers. Deformation vector fields extracted from the 4DMRI, referred to as ground truth motion, were used to generate 4DCT(MRI) data sets of two lung cancer patients, resulting in 10 data sets with variable motion patterns. Given the 4DCT(MRI) and the corresponding ultrasound images as surrogate data, a patient-specific motion model was built. The model consists of an autoregressive model and Gaussian process regression for the temporal and spatial prediction, respectively. Two-field PBS plans were optimised on the reference CTs, and 4D dose calculations (4DDC) were used to simulate dose delivery for (a) unmitigated motion, (b) ideal 2D and 3D tracking (both beam adaption and 4DDC based on ground truth motion), and (c) realistic 2D and 3D tracking (beam adaption based on motion predictions, 4DDC on ground truth motion). Model-guided tracking retrieved clinically acceptable target dose homogeneity, as seen in a substantial reduction of the D5%-D95% compared to the non-mitigated simulation. Tracking in 2D and 3D resulted in a similar improvement of the dose homogeneity, as did ideal and realistic tracking simulations. In some cases, however, the tracked deliveries resulted in a shift towards higher or lower dose levels, leading to unacceptable target over- or under-coverage. The presented motion modelling framework was shown to be an accurate motion prediction tool for the use in proton beam tracking. Tracking alone, however, may not always effectively mitigate motion effects, making it necessary to combine it with other techniques such as rescanning.