Evolution of peripheral nerve changes in early multiple sclerosis-a longitudinal MR neurography study.

Objectives: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system. Increasing evidence indicates additional peripheral nerve involvement in early and chronic disease stages. To investigate the evolution of peripheral nerve changes in patients first diagnosed with MS using quantitative MR neurography. Materials and methods: This prospective study included 19 patients with newly diagnosed MS according to the revised McDonald criteria (16 female, mean 30.2 ± 7.1 years) and 19 age-/sex-matched healthy volunteers. High-resolution 3 T MR neurography of the sciatic nerve using a quantitative T2-relaxometry sequence was performed, which yielded the biomarkers of T2 relaxation time (T2app) and proton spin density (PSD). Follow-up scans of patients were performed after median of 12 months (range 7-16). Correlation analyses considered clinical symptoms, intrathecal immunoglobulin synthesis, nerve conduction study, and lesion load on brain and spine MRI. Results: Patients showed increased T2app and decreased PSD compared to healthy controls at initial diagnosis and follow-up (p < 0.001 each). Compared to the initial scan, T2app further increased in patients at follow-up (p = 0.003). PSD further declined by at least 10% in 9/19 patients and remained stable in another 9/19 patients. Correlation analyses did not yield significant results. Conclusion: Peripheral nerve involvement in MS appears at initial diagnosis and continues to evolve within 1 year follow-up with individual dynamics. Quantitative MRN provides non-invasive biomarkers to detect and monitor peripheral nerve changes in MS.

Diffusion tensor imaging in anisotropic tissues: application of reduced gradient vector schemes in peripheral nerves.

BACKGROUND: In contrast to the brain, fibers within peripheral nerves have distinct monodirectional structure questioning the necessity of complex multidirectional gradient vector schemes for DTI. This proof-of-concept study investigated the diagnostic utility of reduced gradient vector schemes in peripheral nerve DTI. METHODS: Three-Tesla magnetic resonance neurography of the tibial nerve using 20-vector DTI (DTI20) was performed in 10 healthy volunteers, 12 patients with type 2 diabetes, and 12 age-matched healthy controls. From the full DTI20 dataset, three reduced datasets including only two or three vectors along the x- and/or y- and z-axes were built to calculate major parameters. The influence of nerve angulation and intraneural connective tissue was assessed. The area under the receiver operating characteristics curve (ROC-AUC) was used for analysis. RESULTS: Simplified datasets achieved excellent diagnostic accuracy equal to DTI20 (ROC-AUC 0.847-0.868, p ≤ 0.005), but compared to DTI20, the reduced models yielded mostly lower absolute values of DTI scalars: median fractional anisotropy (FA) ≤ 0.12; apparent diffusion coefficient (ADC) ≤ 0.25; axial diffusivity ≤ 0.96, radial diffusivity ≤ 0.07). The precision of FA and ADC with the three-vector model was closest to DTI20. Intraneural connective tissue was negatively correlated with FA and ADC (r ≥ -0.49, p < 0.001). Small deviations of nerve angulation had little effect on FA accuracy. CONCLUSIONS: In peripheral nerves, bulk tissue DTI metrics can be approximated with only three predefined gradient vectors along the scanner's main axes, yielding similar diagnostic accuracy as a 20-vector DTI, resulting in substantial scan time reduction. RELEVANCE STATEMENT: DTI bulk tissue parameters of peripheral nerves can be calculated with only three predefined gradient vectors at similar diagnostic performance as a standard DTI but providing a substantial scan time reduction. KEY POINTS: • In peripheral nerves, DTI parameters can be approximated using only three gradient vectors. • The simplified model achieves a similar diagnostic performance as a standard DTI. • The simplified model allows for a significant acceleration of image acquisition. • This can help to introduce multi-b-value DTI techniques into clinical practice.

Microstructural changes of peripheral nerves in early multiple sclerosis: A prospective magnetic resonance neurography study.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS). However, there is increasing evidence of peripheral nerve involvement. This study aims to characterize the pattern of peripheral nerve changes in patients with newly diagnosed MS using quantitative magnetic resonance (MR) neurography. METHODS: In this prospective study, 25 patients first diagnosed with MS according to the revised McDonald criteria (16 female, mean age = 32.8 ± 10.6 years) and 14 healthy controls were examined with high-resolution 3-T MR neurography of the sciatic nerve using diffusion kurtosis imaging (DKI; 20 diffusional directions, b = 0, 700, 1200 s/mm2 ) and magnetization transfer imaging (MTI). In total, 15 quantitative MR biomarkers were analyzed and correlated with clinical symptoms, intrathecal immunoglobulin synthesis, electrophysiology, and lesion load on brain and spine MR imaging. RESULTS: Patients showed decreased fractional anisotropy (mean = 0.51 ± 0.04 vs. 0.56 ± 0.03, p < 0.001), extra-axonal tortuosity (mean = 2.32 ± 0.17 vs. 2.49 ± 0.17, p = 0.008), and radial kurtosis (mean = 1.40 ± 0.23 vs. 1.62 ± 0.23, p = 0.014) and higher radial diffusivity (mean = 1.09 ∙ 10-3 mm2 /s ± 0.16 vs. 0.98 ± 0.11 ∙ 10-3 mm2 /s, p = 0.036) than controls. Groups did not differ in MTI. No significant association was found between MR neurography markers and clinical/laboratory parameters or CNS lesion load. CONCLUSIONS: This study provides further evidence of peripheral nerve involvement in MS already at initial diagnosis. The characteristic pattern of DKI parameters indicates predominant demyelination and suggests a primary coaffection of the peripheral nervous system in MS. This first human study using DKI for peripheral nerves shows its potential and clinical feasibility in providing novel biomarkers.

Quantitative MR Neurography in Multifocal Motor Neuropathy and Amyotrophic Lateral Sclerosis.

BACKGROUND: The aim of this study was to assess the phenotype of multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) in quantitative MR neurography. METHODS: In this prospective study, 22 patients with ALS, 8 patients with MMN, and 10 healthy volunteers were examined with 3T MR neurography, using a high-resolution fat-saturated T2-weighted sequence, diffusion-tensor imaging (DTI), and a multi-echo T2-relaxometry sequence. The quantitative biomarkers fractional anisotropy (FA), radial and axial diffusivity (RD, AD), mean diffusivity (MD), cross-sectional area (CSA), T2-relaxation time, and proton spin density (PSD) were measured in the tibial nerve at the thigh and calf, and in the median, radial, and ulnar nerves at the mid-upper arm. RESULTS: MMN showed a characteristic imaging pattern of decreased FA (p = 0.018), increased RD (p = 0.014), increased CSA (p < 0.001), increased T2-relaxation time (p < 0.001), and increased PSD (p = 0.025) in the upper arm nerves compared to ALS and controls. ALS patients did not differ from controls in any imaging marker, nor were there any group differences in the tibial nerve (p > 0.05). CONCLUSIONS: MMN shows a characteristic pattern of quantitative DTI and T2-relaxometry parameters in the upper-arm nerves, primarily indicating demyelination. Peripheral nerve changes in ALS seem to be below the detection level of current state-of-the-art quantitative MR neurography.

Peripheral Nerve Involvement at First Diagnosis of Multiple Sclerosis: A Prospective MR Neurography Study.

OBJECTIVES: The aim of this study was to assess peripheral nerve involvement in patients with multiple sclerosis (MS) at first clinical presentation using quantitative magnetic resonance (MR) neurography in correlation with clinical, laboratory, electrophysiological, and central nervous MR imaging data. MATERIALS AND METHODS: In this prospective monocentric study, 30 patients first diagnosed with MS according to the McDonald criteria (19 women; mean age, 32.4 ± 8.8 years) and 30 age- and sex-matched healthy volunteers were examined with high-resolution 3 T MR neurography using a dual-echo T2-relaxometry sequence covering the tibial and peroneal nerves from proximal thigh to distal calf. Magnetic resonance biomarkers of T2 relaxation time (T2 app ), proton spin density (PSD), and nerve cross-sectional area (CSA) were correlated with clinical symptoms, intrathecal immunoglobulin (Ig) synthesis, nerve conduction study, and lesion load on brain and spine MR imaging. The diagnostic accuracy of MR biomarkers was assessed using receiver-operating characteristic curves. RESULTS: Diffuse nerve changes were detected along the tibial and peroneal nerves in MS patients, who showed decreased PSD ( P < 0.001), increased T2 app ( P < 0.001), and smaller tibial nerve CSA ( P < 0.001) compared with healthy subjects. Tibial PSD was identified as best parameter separating patients from controls (area under the curve = 0.876). Intrathecal IgG and IgM synthesis correlated with PSD values ( r = -0.44, P = 0.016, and r = -0.42, P = 0.022). Contrast-enhancement of brain or spine lesions was related to larger tibial and peroneal CSA ( P < 0.001, P = 0.033). Abnormal electrophysiology correlated with higher tibial and peroneal T2 app ( P < 0.001 and P = 0.033), lower tibial and peroneal PSD ( P = 0.018 and P = 0.002), and smaller peroneal CSA ( P < 0.001). CONCLUSIONS: Quantitative MR neurography reveals peripheral nerve changes in patients with initial diagnosis of MS. Correlation of imaging findings with intrathecal immunoglobulin synthesis may indicate a primary coaffection of the peripheral nervous system in MS.

Quantitative MR-Neurography at 3.0T: Inter-Scanner Reproducibility.

BACKGROUND: Quantitative MR-neurography (MRN) is increasingly applied, however, the impact of the MR-scanner on the derived parameters is unknown. Here, we used different 3.0T MR scanners and applied comparable MR-sequences in order to quantify the inter-scanner reproducibility of various MRN parameters of the sciatic nerve. METHODS: Ten healthy volunteers were prospectively examined at three different 3.0T MR scanners and underwent MRN of their sciatic nerve using comparable imaging protocols including diffusion tensor imaging (DTI) and T2 relaxometry. Subsequently, inter-scanner agreement was assessed for seven different parameters by calculating the intraclass correlation coefficients (ICCs) and the standard error of measurement (SEM). RESULTS: Assessment of inter-scanner reliability revealed good to excellent agreement for T2 (ICC: 0.846) and the quantitative DTI parameters, such as fractional anisotropy (FA) (ICC: 0.876), whereas moderate agreement was observed for proton spin density (PD) (ICC: 0.51). Analysis of variance identified significant inter-scanner differences for several parameters, such as FA (p < 0.001; p = 0.02), T2 (p < 0.01) and PD (p = 0.02; p < 0.01; p = 0.02). Calculated SEM values were mostly within the range of one standard deviation of the absolute mean values, for example 0.033 for FA, 4.12 ms for T2 and 27.8 for PD. CONCLUSION: This study quantifies the measurement imprecision for peripheral nerve DTI and T2 relaxometry, which is associated with the use of different MR scanners. The here presented values may serve as an orientation of the possible scanner-associated fluctuations of MRN biomarkers, which can occur under similar conditions.

Imaging visuospatial memory in temporal lobe epilepsy-Results of an fMRI study.

PURPOSE: Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland's Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. METHODS: We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). RESULTS: Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. CONCLUSION: While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

Neuroradiological differentiation of white matter lesions in patients with multiple sclerosis and Fabry disease.

OBJECTIVE: White matter lesions (WML) in multiple sclerosis (MS) differ from vascular WML caused by Fabry disease (FD). However, in atypical cases the discrimination can be difficult and may vary between individual raters. The aim of this study was to evaluate interrater reliability of WML differentiation between MS and FD patients. MATERIALS AND METHODS: Brain MRI scans of 21 patients with genetically confirmed FD were compared to 21 matched patients with MS. Pseudonymized axial FLAIR sequences were assessed by 6 blinded raters and attributed to either the MS or the FD group to investigate interrater reliability. Additionally, localization of WML was compared between the two groups. RESULTS: The median age of patients was 46 years (IQR 35-58). Interrater reliability was moderate with a Fleiss' Kappa of 0.45 (95%CI 0.3-0.59). Overall, 85% of all ratings in the MS group and 75% in the FD group were correct. However, only 38% of patients with MS and 33% of patients with FD were correctly identified by all 6 raters. WML involving the corpus callosum (p < 0.001) as well as juxtacortical (p < 0.001) and infratentorial lesions (p = 0.03) were more frequently observed in MS patients. CONCLUSION: Interrater reliability regarding visual differentiation of WML in MS from vascular WML in FD on standard axial FLAIR images alone is only moderate, despite the distinctive features of lesions in each group.

Diffusion MRI in Peripheral Nerves: Optimized b Values and the Role of Non-Gaussian Diffusion.

Background Diffusion-weighted imaging (DWI) provides specific in vivo information about tissue microstructure, which is increasingly recognized for various applications outside the central nervous system. However, standard sequence parameters are commonly adopted from optimized central nervous system protocols, thus potentially neglecting differences in tissue-specific diffusional behavior. Purpose To characterize the optimal tissue-specific diffusion imaging weighting scheme over the b domain in peripheral nerves under physiologic and pathologic conditions. Materials and Methods In this prospective cross-sectional study, 3-T MR neurography of the sciatic nerve was performed in healthy volunteers (n = 16) and participants with type 2 diabetes (n = 12). For DWI, 16 b values in the range of 0-1500 sec/mm2 were acquired in axial and radial diffusion directions of the nerve. With a region of interest-based approach, diffusion-weighted signal behavior as a function of b was estimated using standard monoexponential, biexponential, and kurtosis fitting. Goodness of fit was assessed to determine the optimal b value for two-point DWI/diffusion tensor imaging (DTI). Results Non-Gaussian diffusional behavior was observed beyond b values of 600 sec/mm2 in the axial and 800 sec/mm2 in the radial diffusion direction in both participants with diabetes and healthy volunteers. Accordingly, the biexponential and kurtosis models achieved a better curve fit compared with the standard monoexponential model (Akaike information criterion >99.9% in all models), but the kurtosis model was preferred in the majority of cases. Significant differences between healthy volunteers and participants with diabetes were found in the kurtosis-derived parameters Dk and K. The results suggest an upper bound b value of approximately 700 sec/mm2 for optimal standard DWI/DTI in peripheral nerve applications. Conclusion In MR neurography, an ideal standard diffusion-weighted imaging/diffusion tensor imaging protocol with b = 700 sec/mm2 is suggested. This is substantially lower than in the central nervous system due to early-occurring non-Gaussian diffusion behavior and emphasizes the need for tissue-specific b value optimization. Including higher b values, kurtosis-derived parameters may represent promising novel imaging markers of peripheral nerve disease. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Jang and Du in this issue.

Reliability and reproducibility of sciatic nerve magnetization transfer imaging and T2 relaxometry.

OBJECTIVES: To assess the interreader and test-retest reliability of magnetization transfer imaging (MTI) and T2 relaxometry in sciatic nerve MR neurography (MRN). MATERIALS AND METHODS: In this prospective study, 21 healthy volunteers were examined three times on separate days by a standardized MRN protocol at 3 Tesla, consisting of an MTI sequence, a multi-echo T2 relaxometry sequence, and a high-resolution T2-weighted sequence. Magnetization transfer ratio (MTR), T2 relaxation time, and proton spin density (PSD) of the sciatic nerve were assessed by two independent observers, and both interreader and test-retest reliability for all readout parameters were reported by intraclass correlation coefficients (ICCs) and standard error of measurement (SEM). RESULTS: For the sciatic nerve, overall mean ± standard deviation MTR was 26.75 ± 3.5%, T2 was 64.54 ± 8.2 ms, and PSD was 340.93 ± 78.8. ICCs ranged between 0.81 (MTR) and 0.94 (PSD) for interreader reliability and between 0.75 (MTR) and 0.94 (PSD) for test-retest reliability. SEM for interreader reliability was 1.7% for MTR, 2.67 ms for T2, and 21.3 for PSD. SEM for test-retest reliability was 1.7% for MTR, 2.66 ms for T2, and 20.1 for PSD. CONCLUSIONS: MTI and T2 relaxometry of the sciatic nerve are reliable and reproducible. The values of measurement imprecision reported here may serve as a guide for correct interpretation of quantitative MRN biomarkers in future studies. KEY POINTS: • Magnetization transfer imaging (MTI) and T2 relaxometry of the sciatic nerve are reliable and reproducible. • The imprecision that is unavoidably associated with different scans or different readers can be estimated by the here presented SEM values for the biomarkers T2, PSD, and MTR. • These values may serve as a guide for correct interpretation of quantitative MRN biomarkers in future studies and possible clinical applications.

Language network reorganization before and after temporal lobe epilepsy surgery.

OBJECTIVE: Epilepsy surgery is the recommended treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). This method offers a good chance of seizure freedom but carries a considerable risk of postoperative language impairment. The extremely variable neurocognitive profiles in surgical epilepsy patients cannot be fully explained by extent of resection, fiber integrity, or current task-based functional MRI (fMRI). In this study, the authors aimed to investigate pathology- and surgery-triggered language organization in TLE by using fMRI activation and network analysis as well as considering structural and neuropsychological measures. METHODS: Twenty-eight patients with unilateral TLE (16 right, 12 left) underwent T1-weighted imaging, diffusion tensor imaging, and task-based language fMRI pre- and postoperatively (n = 15 anterior temporal lobectomy, n = 11 selective amygdalohippocampectomy, n = 2 focal resection). Twenty-two healthy subjects served as the control cohort. Functional connectivity, activation maps, and laterality indices for language dominance were analyzed from fMRI data. Postoperative fractional anisotropy values of 7 major tracts were calculated. Naming, semantic, and phonematic verbal fluency scores before and after surgery were correlated with imaging parameters. RESULTS: fMRI network analysis revealed widespread, bihemispheric alterations in language architecture that were not captured by activation analysis. These network changes were found preoperatively and proceeded after surgery with characteristic patterns in the left and right TLEs. Ipsilesional fronto-temporal connectivity decreased in both left and right TLE. In left TLE specifically, preoperative atypical language dominance predicted better postoperative verbal fluency and naming function. In right TLE, left frontal language dominance correlated with good semantic verbal fluency before and after surgery, and left fronto-temporal language laterality predicted good naming outcome. Ongoing seizures after surgery (Engel classes ID-IV) were associated with naming deterioration irrespective of seizure side. Functional findings were not explained by the extent of resection or integrity of major white matter tracts. CONCLUSIONS: Functional connectivity analysis contributes unique insight into bihemispheric remodeling processes of language networks after epilepsy surgery, with characteristic findings in left and right TLE. Presurgical contralateral language recruitment is associated with better postsurgical language outcome in left and right TLE.