Ahmed Radwan

Purpose Although the T1w/T2w ratio was introduced as a proxy for myelin, it may reflect broader aspects of brain tissue health. The recently introduced T1w/FLAIR ratio has yet to be evaluated in relation to biological and clinical markers. This study investigates its association with myelin water fraction (MWF), diffusion MRI (dMRI), and cognitive performance, and explores whether alternative weightings of the ratio improve these associations. Methods 36 women were retrospectively included from a previous study with neuropsychological testing and 3T MRI. Spearman correlations assessed associations between the T1w/FLAIR ratio and MWF, fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), orientation dispersion index (ODI), and fraction of isotropic diffusion compartment (FISO). Region-specific and overall correlations were evaluated across 36 white matter regions, lesions, total white matter, and cortical and deep gray matter. Associations with attention, memory, and processing speed were examined. Least squares regression was used to derive an optimally weighted ratio based on MWF, and analyses were repeated using this weighted ratio. Results Significant correlations between the T1w/FLAIR ratio and MWF and/or dMRI measures were found in six out of 40 regions. Across regions and subjects, the ratio showed weak overall correlations (r < 0.5) with MWF, FA, NDI, and FISO. A significant positive correlation with memory was only observed within lesions. The optimal weighting favored a stronger contribution from the T1w signal but resulted in only slightly stronger correlations. Conclusion Our results support the interpretation of T1w/FLAIR ratio as a general marker of tissue health rather than a specific measure for myelin.

Objective: To evaluate ¹⁸F‐fluorodeoxyglucose ( ¹⁸ F‐FDG) positron emission tomography (PET) as a biomarker in suspected non‐convulsive status epilepticus (NCSE) by characterizing electroclinical‐metabolic correlations and quantifying focal hypermetabolism. Methods: We included adult patients with rhythmic and periodic patterns (RPPs) undergoing ¹⁸ F‐FDG PET for suspected NCSE. Two neurologists reviewed patient electroencephalography (EEG) recordings (0–30 min post‐injection) using 2021 American Clinical Neurophysiology Society (ACNS) criteria. ¹⁸ F‐FDG PET images were blindly assessed by two nuclear medicine specialists for the presence and lobar location of focal hypermetabolism. Structural magnetic resonance imaging (MRI) studies enabled PET co‐registration and segmentation. Patients with available MRI scans were compared to external age/sex‐matched and in‐house validation healthy control datasets. We calculated intra‐subject standardized uptake value (SUV) z ‐scores within the gray matter and then compared this approach to SUV ratio (SUVR) methods (using either the cerebellum or the pons as reference region) using consensus visual assessment as the reference standard. For hypermetabolic volume quantification, we chose the lowest threshold with 100% specificity ( z ≥ 3.0) to eliminate false‐positive volumes, which yielded 62% sensitivity. Resulting volumes were correlated with lateralized periodic discharge (LPD) main modifiers (frequency, prevalence, evolution, plus‐factors). Results: Of 24 adult patients (median age 62 years, 15 female), 17 (71%) had LPDs. Qualitatively, focal hypermetabolism was present in 92% of patients ( n = 22), with strong concordance between visual PET findings and EEG lateralization in patients with LPDs. Twenty‐three patients underwent MRI and were compared to external age/sex‐matched ( n = 23) and in‐house validation ( n = 22) healthy control datasets. Our technique outperformed traditional SUVR methods (AUC = 0.92 vs 0.55–0.64, p < .001) in detecting focal hypermetabolism. In patients with LPDs, hypermetabolic volumes ranged from 0 to 21.4 mL, with substantial volumes (>10 mL) observed across all discharge frequencies. Significance: ¹⁸ F‐FDG‐PET revealed focal hypermetabolism in most suspected NCSE cases, including in cases with equivocal EEG patterns. In patients with LPDs, the extent of focal hypermetabolism was highly variable across different frequencies.

Objective: Diffusion tensor imaging (DTI) showed promising results in diagnosing upper limb neuropathies, but its value in patients with foot drop due to peroneal neuropathy has not yet been investigated. We aim to establish reference values for DTI metrics of the healthy peroneal nerve and to evaluate differences in DTI metrics between patients and healthy controls.Methods: Diffusion-weighted images (DWI) from 22 pathological nerves, 14 asymptomatic patients’ nerves and 65 healthy peroneal nerves were processed for quantitative assessment of fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity and mean diffusivity. Clinical baseline and follow-up data were prospectively collected for all patients.Results: Mean patient FA values (0.40, SD 0.08) were significantly lower compared with healthy controls (mean FA 0.44, SD 0.06). Mean patient RD values (0.98 10⁻³mm²/s, SD 0.21 10⁻³mm²/s) were significantly higher compared with healthy controls (mean RD 0.85 10⁻³mm²/s, SD 0.16 10⁻³mm²/s). FA values were significantly lower in patients with severe foot drop (mean FA 0.40, SD 0.06) compared with non-severe foot drop (mean FA 0.48, SD 0.05).Conclusion: Based on these results, DTI appears to aid in the differential diagnostic process of patients with peroneal neuropathy. Future studies should focus on automation of DWI processing, confirm the results in larger patient groups and try to establish reliable cut-off values for DTI metrics.

Lesion characteristics (e.g., types, extents, and locations) vary widely in patients with moderate to severe Traumatic Brain Injury (ms-TBI). Automated tools for parcellating anatomical MRI scans, such as FastSurfer, assume the input brain has normal anatomy. Thus, heterogeneous lesions often cause parcellation errors. In this lesion simulation study, we test whether a recently developed lesion filling tool (Virtual Brain Grafting, VBG) reduces FastSurfer parcellation errors. T1-weighted (T1w) magnetic resonance images (MRIs) were obtained from 140 healthy controls and 14 ms-TBI patients from the ENIGMA TBI working group. Binary masks indexing focal lesions (ranging from small [38mm3] unilateral, to large [164,291mm3] bilateral lesions) in the ms-TBI patients were each projected onto 10 healthy control T1w MRIs, creating a group of 140 synthetically lesioned images (lesions from 14 patients x 10 HCs T1w images). VBG was used to fill lesioned images with simulated healthy brain tissue, creating 140 VBG-filled images. A third set of lesion-free images were created in the same anatomical space, to be used as the “ground truth” against which to compare the lesioned and VBG-filled images. FastSurfer was used to parcellate the cortex. The accuracy of VBG filling was assessed qualitatively through visual inspection. Mean Dice Similarity Coefficients (DSC) and Percent Volume Differences (PVD) between lesioned and lesion-free images were compared to DSC and PVD scores between VBG-filled and lesion-free images, using paired sample t-tests.VBG-filled images predominantly showed anatomically plausible filling. However, several distinct boundaries and visible textural differences were observed, especially for lesions on the cortical ribbon. Near large focal lesions, VBG-filled images appeared more similar than the lesioned images to the ground truth (lesion-free images). Contrary to expectations, parcellations from lesioned images (DSC M = 0.93, SD = 0.03; PVD M = -0.40, SD = 1.7) had significantly higher DSCs [t(111) = 19.5, p < 0.001], and lower PVDs [t(111) = 11.3, p < 0.001] with the parcellations from the lesion-free images, compared to the parcellations from VBG-filled images (DSC M = 0.81, SD = 0.07; PVD M = -9.03, SD = 7.72). In other words, the parcellations from the lesioned images had closer spatial alignment and volume measurements were in greater agreement with the lesion-free (ground truth) images, when compared to VBG-filled images. This unexpected finding might be due to a high frequency of smaller focal lesions in our TBI patients and a possible improvement in FastSurfer parcellations when encountering such lesions. VBG was not developed for lesions caused by TBI, and thus a lesion filling tool is needed that specifically addresses the heterogeneity of lesions observed in ms-TBI.

Resting-state functional MRI (rsfMRI) could enable preoperative risk assessment and intraoperative guidance for patients who cannot undergo task-based fMRI (tbfMRI). To ascertain rsfMRI’s applicability, we investigated differences in accuracy between tbfMRI with a voxel size of 1.8 x 1.8 x 3.2 mm³ and rsfMRI acquired with single-echo (sTE) with a voxel size of 2 x 2 x 2.2 mm³ and multiecho (mTE) with a voxel size of 3 x 3 x 3 mm³ using intraoperative mapping with direct electrical stimulations (DES) as the ground truth. Functional sensory-motor mapping results of hands and feet were spatially compared relative to positive (pDES, functional effect) and negative (nDES, no functional effect) coordinates in 16 preoperative patients. A general linear model analysis was used for tbfMRI, and seed-based analysis (SBA) for rsfMRI. Minimum Euclidean distances between fMRI and DES were calculated and compared between fMRI methods. Receiver-operating characteristic (ROC) curves were used to compare accuracy and determine distance cutoffs for fMRI agreement with DES, and binary agreement rates were compared at different cutoffs. Two-part mixed-effects linear models were used to compare fMRI methods while accounting for unequal intersubject DES repetition. Only minor differences were found between fMRI methods in unthresholded distances (mean differences ~2 mm). ROCs and binary agreement measures showed comparable accuracy for tbfMRI and sTE-rsfMRI at 2 mm, but mildly worse for sTE-rsfMRI at 3 mm and mTE-rsfMRI. However, differences in relative accuracy between sTE-rsfMRI and mTE-rsfMRI were minor when the same distance cutoff was applied to all methods. This was also reflected in comparing binary agreement rates and confirmed by the two-part linear models, which showed no significant differences between fMRI methods and a significant effect of DES response. A similar accuracy for SBA rsfMRI functional sensory-motor mapping compared with tbfMRI for the hands and feet indicates that rsfMRI may be suitable for presurgical mapping. The differences in relative accuracy between sTE-rsfMRI and mTE-rsfMRI warrant further investigation in a larger sample.

Objectives: Accurate presurgical brain mapping enables preoperative risk assessment and intraoperative guidance. This cross‐sectional study investigated whether constrained spherical deconvolution (CSD) methods were more accurate than diffusion tensor imaging (DTI)‐based methods for presurgical white matter mapping using intraoperative direct electrical stimulation (DES) as the ground truth.Methods: Five different tractography methods were compared (three DTI‐based and two CSD‐based) in 22 preoperative neurosurgical patients undergoing surgery with DES mapping. The corticospinal tract (CST, N = 20) and arcuate fasciculus (AF, N = 7) bundles were reconstructed, then minimum distances between tractograms and DES coordinates were compared between tractography methods. Receiver‐operating characteristic (ROC) curves were used for both bundles. For the CST, binary agreement, linear modeling, and posthoc testing were used to compare tractography methods while correcting for relative lesion and bundle volumes.Results: Distance measures between 154 positive (functional response, pDES) and negative (no response, nDES) coordinates, and 134 tractograms resulted in 860 data points. Higher agreement was found between pDES coordinates and CSD‐based compared to DTI‐based tractograms. ROC curves showed overall higher sensitivity at shorter distance cutoffs for CSD (8.5 mm) compared to DTI (14.5 mm). CSD‐based CST tractograms showed significantly higher agreement with pDES, which was confirmed by linear modeling and posthoc tests (P_FWE < .05).Conclusions: CSD‐based CST tractograms were more accurate than DTI‐based ones when validated using DES‐based assessment of motor and sensory function. This demonstrates the potential benefits of structural mapping using CSD in clinical practice.

Introduction: Resting-state functional MRI (rs-fMRI) could enable preoperative risk assessment and intraoperative guidance for patients who cannot undergo task-based fMRI (tbfMRI). We investigated differences in accuracy between tbfMRI and rsfMRI acquired with single (sTE) at voxel size of 2mm and 3mm, and multi-echo (mTE) scans using intraoperative mapping with direct electrical stimulations (DES) as the ground truth. Material and methods: Functional sensory-motor mapping results of hands and feet were spatially compared relative to positive (pDES, functional effect) and negative (nDES, no functional effect) coordinates in 16 preoperative patients. General linear model analysis was used for tbfMRI, and seed-based analysis (SBA) for rsfMRI. Minimum Euclidean distances between fMRI and DES were calculated and compared between fMRI methods. Receiver-operating characteristic (ROC) curves were used to compare accuracy and determine distance cutoffs for fMRI agreement with DES, and binary agreement rates were compared at different cutoffs. Two-part mixed-effects linear models were used to compare fMRI methods while accounting for unequal inter-subject DES repetition. Results: Only minor differences were found between fMRI methods in unthresholded distances (mean differences ∼ 2 mm). ROCs and binary agreement measures showed comparable accuracy for tbfMRI and sTE-rsfMRI 2mm, but mildly worse for sTE-rsfMRI 3mm and mTE-rsfMRI. However, differences in relative accuracy between sTE- and mTE-rsfMRI were minor when the same distance cutoff was applied to all methods. This was also reflected on comparing rates of binary agreement and confirmed by the two-part linear models, which showed no significant differences between fMRI methods and a significant effect of DES response. Conclusion: The similar accuracy for SBA rsfMRI functional sensory-motor mapping compared to tbfMRI for the hands and feet, indicate that rsfMRI may be suitable for presurgical mapping. The differences in relative accuracy between sTE- and mTE rsfMRI warrant further investigation in a larger sample.

COVID-19 can induce neurological sequelae, negatively affecting the quality of life. Unravelling this illness's impact on structural brain connectivity, white-matter microstructure (WMM), and cognitive performance may help elucidate its implications. This cross-sectional study aimed to investigate differences in these factors between former hospitalised COVID-19 patients (COV) and healthy controls. Group differences in structural brain connectivity were explored using Welch-two sample t-tests and two-sample Mann–Whitney U tests. Multivariate linear models were constructed (one per region) to examine fixel-based group differences. Differences in cognitive performance between groups were investigated using Wilcoxon Rank Sum tests. Possible effects of bundle-specific FD measures on cognitive performance were explored using a two-group path model. No differences in whole-brain structural organisation were found. Bundle-specific metrics showed reduced fiber density (p = 0.012, Hedges’ g = 0.884) and fiber density cross-section (p = 0.007, Hedges’ g = 0.945) in the motor segment of the corpus callosum in COV compared to healthy controls. Cognitive performance on the motor praxis and digit symbol substitution tests was worse in COV than healthy controls (p < 0.001, r = 0.688; p = 0.013, r = 422, respectively). Associations between the cognitive performance and bundle-specific FD measures differed significantly between groups. WMM and cognitive performance differences were observed between COV and healthy controls.