C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis.

Schwannomatosis is the third form of neurofibromatosis and characterized by the occurrence of multiple schwannomas. The most prominent symptom is chronic pain. We aimed to test whether pain in schwannomatosis might be caused by small-fiber neuropathy. Twenty patients with schwannomatosis underwent neurological examination and nerve conduction studies. Levels of pain perception as well as anxiety and depression were assessed by established questionnaires. Quantitative sensory testing (QST) and laser-evoked potentials (LEP) were performed on patients and controls. Whole-body magnetic resonance imaging (wbMRI) and magnetic resonance neurography (MRN) were performed to quantify tumors and fascicular nerve lesions; skin biopsies were performed to determine intra-epidermal nerve fiber density (IENFD). All patients suffered from chronic pain without further neurological deficits. The questionnaires indicated neuropathic symptoms with significant impact on quality of life. Peripheral nerve tumors were detected in all patients by wbMRI. MRN showed additional multiple fascicular nerve lesions in 16/18 patients. LEP showed significant faster latencies compared to normal controls. Finally, IENFD was significantly reduced in 13/14 patients. Our study therefore indicates the presence of small-fiber neuropathy, predominantly of unmyelinated C-fibers. Fascicular nerve lesions are characteristic disease features that are associated with faster LEP latencies and decreased IENFD. Together these methods may facilitate differential diagnosis of schwannomatosis.

Amyotrophic Lateral Sclerosis versus Multifocal Motor Neuropathy: Utility of MR Neurography.

Background Differential diagnosis between amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy (MMN) relies on clinical examination and electrophysiological criteria. Peripheral nerve imaging might assist this differential diagnosis. Purpose To assess diagnostic accuracy of MR neurography in the differential diagnosis of ALS and MMN. Materials and Methods This prospective study was conducted between December 2015 and April 2017. Study participants with ALS or MMN underwent MR neurography of the lumbosacral plexus, midthigh, proximal calf, and midupper arm of the clinically more affected side using high-resolution T2-weighted sequences. Matched healthy study participants who underwent MR neurography served as a control group. Two blinded readers independently rated fascicular lesions and muscle denervation signs on a five-point scale and made an image-only diagnosis, which was compared with the clinical diagnosis to assess diagnostic accuracy (reported for ALS vs non-ALS and MMN vs non-MMN). The Kruskal-Wallis test was used to compare readers' scoring results. Results Twenty-two participants with ALS (12 men and 10 women; mean age ± standard deviation, 62.3 years ± 9.0), eight participants with MMN (seven men and one woman; mean age, 57.6 years ± 18.6), and 15 healthy participants (seven men and eight women; mean age, 59.1 years ± 10.9) were enrolled in this study. Nerves of participants with ALS either appeared normal or showed T2-weighted hyperintensities without fascicular enlargement (reader 1, 22 of 22 participants; reader 2, 21 of 22 participants). In contrast, nerves in MMN were characterized by fascicular swellings (reader 1, six of eight participants; reader 2, seven of eight participants). Muscle denervation signs were more prominent in ALS than in MMN. Inter-rater reliability for blinded diagnosis was κ of 0.82. By consensus, the sensitivity to diagnose ALS (vs MMN and healthy control participants) was 19 of 22 (86% [95% confidence interval {CI}: 67%, 95%]). The corresponding specificity was 23 of 23 (100% [95% CI: 86%, 100%]). The sensitivity to diagnose MMN (vs ALS and healthy control participants) was seven of eight (88% [95% CI: 53%, 99%]). The corresponding specificity was 37 of 37 (100% [95% CI: 91%, 100%]). Conclusion MR neurography is an accurate method for assisting in the differential diagnosis of amyotrophic lateral sclerosis and multifocal motor neuropathy. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Andreisek in this issue.

Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2.

Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes, and peripheral neuropathy has been reported in both. We prospectively applied in vivo morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis patients, 14 neurofibromatosis type 2 patients, and 26 healthy controls by magnetic resonance neurography. Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in neurofibromatosis type 2 (L3, + 267%; L4, + 235%; L5, + 241%; S1, + 300%; S2, + 242%; Bonferroni-adjusted p < 0.001) but not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in origination of areflexia and sensory loss and a useful diagnostic marker in neurofibromatosis type 2. Ann Neurol 2018;83:854-857.

Susceptibility-weighted imaging in malignant melanoma brain metastasis.

BACKGROUND: The value of cerebral susceptibility-weighted imaging (SWI) in malignant melanoma (MM) patients remains controversial and the effect of melanin on SWI is not well understood. PURPOSE: To systematically analyze the spectrum of intracerebral findings in MM brain metastases (BM) on SWI and to determine the diagnostic value of SWI. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: In all, 100 patients with melanoma BM (69 having received radiotherapy [RT] and 31 RT-naïve) and a control group of 100 melanoma patients without BM were included. For detailed analysis of signal characteristics, 175 metastases were studied. FIELD STRENGTH/SEQUENCE: Gradient echo SWI sequence at 1.5, 3.0, and 9.4 T. ASSESSMENT: Signal characteristics from melanotic and amelanotic BMs on SWI with a focus on blooming artifacts were analyzed, as well as the presence and longitudinal dynamics of isolated SWI blooming artifacts in patients with and without BM. STATISTICAL TESTS: Chi-squared and Student's t-test were used for contingency table measures and group data of signal and clinical characteristics, respectively. RESULTS: Melanotic and amelanotic metastases did not show significant differences of SWI blooming artifacts (38% vs. 43%, P = 0.61). Most metastases without an initial SWI artifact developed a signal dropout during follow-up (80%; 65/81). Isolated SWI artifacts were detected more frequently in patients with BM (20 vs. 9, P = 0.03), of which the majority were found in patients who had received RT (17 vs. 3, P = 0.08). None of these isolated SWI blooming artifacts turned into overt metastases over time (median follow-up: 8.5 months). Similar findings persisted as remnants of successfully treated metastases (88%; 7/8). DATA CONCLUSION: We conclude that SWI provides little additional diagnostic benefit over standard T1 -weighted imaging, as melanin content alone does not cause diagnostically relevant SWI blooming. Signal transition of SWI may rather indicate secondary phenomena like microbleeding and/or metal scavenging. Our results suggest that isolated SWI artifacts do not constitute vital tumor tissue but represent unspecific microbleedings, RT-related parenchymal changes or posttherapeutic remnants of former metastatic lesions. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1251-1259.

Prevalence of fascicular hyperintensities in peripheral nerves of healthy individuals with regard to cerebral white matter lesions.

OBJECTIVE: Detection and pattern analysis of fascicular nerve hyperintensities in the T2-weighted image are the backbone of magnetic resonance neurography (MRN) as they may represent lesions of various etiologies. The aim of this study was to assess the prevalence of fascicular nerve hyperintensities in healthy individuals with regard to a potential association with age or cerebral white matter lesions. METHODS: Sixty volunteers without peripheral nerve diseases between the age of 20 and 80 underwent MRN (high-resolution T2-weighted) of upper (median, ulnar, radial) and lower (sciatic, tibial) extremity nerves and a fluid-attenuated inversion recovery (FLAIR) sequence of the brain. Presence of peripheral nerve hyperintensities and degree of cerebral white matter lesions were independently rated by two blinded readers and related to each other and to age. T test with Welch's correction was used for group comparisons. Spearman's correlation coefficients were reported for correlation analyses. RESULTS: MR neurography revealed fascicular hyperintensities in 10 of 60 subjects (16.7%). Most frequently, they occurred in the sciatic nerve (8/60 subjects, 13.3%), less frequently in the tibial nerve at the lower leg and the median, ulnar, and radial nerves at the upper arm (1.7-5.0%). Mean age of subjects with nerve hyperintensities was higher than that of those without (60.6 years vs. 48.0 years, p = 0.038). There was only a weak correlation of nerve lesions with age and with cerebral white matter lesions, respectively. CONCLUSION: Fascicular nerve hyperintensities may occur in healthy individuals and should therefore always be regarded in conjunction with the clinical context. KEY POINTS: • MR neurography may reveal fascicular hyperintensities in peripheral nerves of healthy individuals. Fascicular hyperintensities occur predominantly in the sciatic nerve and older individuals. • Therefore, fascicular hyperintensities should only be interpreted as clearly pathologic in conjunction with the clinical context.

Peripheral nerve diffusion tensor imaging (DTI): normal values and demographic determinants in a cohort of 60 healthy individuals.

OBJECTIVE: To identify demographic determinants of peripheral nerve diffusion tensor imaging (DTI) and to establish normal values for fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). METHODS: Sixty subjects were examined at 3 Tesla by single-shot DTI. FA, AD, RD, and MD were collected for the sciatic, tibial, median, ulnar, and radial nerve and were correlated with demographic variables. RESULTS: Mean FA of all nerves declined with increasing age (r = -0.77), which could be explained by RD increasing (r = 0.56) and AD declining (r = -0.40) with age. Moreover, FA was inversely associated with height (r = -0.28), weight (r = -0.38) and BMI (r = -0.35). Although FA tended to be lower in men than women (p = 0.052), this difference became completely negligible after adjustment to body weight. A multiple linear regression model for FA was calculated with age and weight as predictors (defined by backward variable selection), yielding an R 2 = 0.71 and providing a correction formula to adjust FA for age and weight. CONCLUSION: Peripheral nerve DTI parameters depend on demographic variables. The most important determinants age and weight should be considered in all studies employing peripheral nerve DTI. KEY POINTS: • Peripheral nerve diffusion tensor imaging (DTI) parameters depend on demographic variables. • Fractional anisotropy (FA) declines with increasing age and weight. • Gender does not systematically affect peripheral nerve DTI. • The formula presented here allows adjustment of FA for demographic variables.

Pediatric Brain: No Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-weighted MR Images after Consecutive Exposure to a Macrocyclic Gadolinium-based Contrast Agent.

Purpose To determine the effect of at least five serial injections of the macrocyclic gadolinium-based contrast agent (GBCA) gadoterate meglumine on the signal intensity (SI) of the dentate nucleus (DN) of the pediatric brain on nonenhanced T1-weighted magnetic resonance (MR) images. Materials and Methods In this retrospective, institutional review board-approved study, 41 pediatric patients (age range, 3-17 years) who were imaged in at least five consecutive 1.5-T MR examinations with the exclusive use of gadoterate meglumine (plus a final additional nonenhanced MR imaging examination) were evaluated. SI ratio differences between the first and last MR examination were calculated for DN-to-pons and DN-to-middle cerebellar peduncle (MCP) ratios in a region-of-interest-based analysis, and one-sample t tests were used to examine if the SI ratio differences differed from 0. Bayes factors were calculated to quantify the strength of evidence for each test. Results Patients underwent a mean of 8.6 ± 3.9 GBCA administrations (mean accumulated dose, 32.07 mmol ± 17.62, with an average of 16.7 weeks ± 7.9 between every administration). Both ratio differences did not differ significantly from 0 (DN-to-pons ratio: -0.0012 ± 0.0101, P = .436; DN-to-MCP ratio: 0.0007 ± 0.0088, P = .604), and one-sided Bayes factors provided substantial evidence against an SI ratio increase (0.10 for DN-to-pons ratio; 0.27 for DN-to-MCP ratio). Conclusion No increase of the SI in the DN was found after a mean of 8.6 serial injections of the macrocyclic GBCA gadoterate meglumine in pediatric patients, confirming previous studies that did not find this effect after serial injections of macrocyclic GBCAs in adults. © RSNA, 2017.

T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain.

Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P < .0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.

Multifocal nerve lesions and LZTR1 germline mutations in segmental schwannomatosis.

Schwannomatosis is a genetic disorder characterized by the occurrence of multiple peripheral schwannomas. Segmental schwannomatosis is diagnosed when schwannomas are restricted to 1 extremity and is thought to be caused by genetic mosaicism. We studied 5 patients with segmental schwannomatosis through microstructural magnetic resonance neurography and mutation analysis of NF2, SMARCB1, and LZTR1. In 4 of 5 patients, subtle fascicular nerve lesions were detected in clinically unaffected extremities. Two patients exhibited LZTR1 germline mutations. This appears contrary to a simple concept of genetic mosaicism and suggests more complex and heterogeneous mechanisms underlying the phenotype of segmental schwannomatosis than previously thought. Ann Neurol 2016;80:625-628.

Human dorsal-root-ganglion perfusion measured in-vivo by MRI.

PURPOSE: To develop an in-vivo imaging method for the measurement of dorsal-root-ganglia-(DRG) perfusion, to establish its normal values in patients without known peripheral nerve disorders or radicular pain syndromes and to determine the physiological spatial perfusion pattern within the DRG. METHODS: This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 46 (24 female, 22 male, mean age 46.0±15.2years) subjects without known peripheral neuropathies or pain syndromes were examined by a 3Tesla MRI scanner (Magnetom VERIO or TRIO, Siemens AG, Erlangen, Germany) with a VIBE (Volume-Interpolated-Breathhold-Examination) dynamic-contrast-enhanced (DCE) T1-w-sequence (TR/TE 3.3/1.11ms; 24 slices; voxel resolution 1.3×1.3×3.0mm(3)) covered the pelvis from the upper plate of the 5th lumbar vertebra to the 2nd sacral vertebra. Transfer-constant (K(trans)) and interstitial-volume-fraction (interstitial-leakage-fraction, Ve) were modeled for the DRG and spinal nerve by applying the Tofts-model. Statistical analyses included pairwise comparisons of L5/S1 DRG vs. spinal nerve. Furthermore, distinct physiological zones within the S1 DRG were compared (cell body rich area (CBRA) vs. nerve fiber rich area (NFRA)). RESULTS: DRG showed a significantly increased permeability compared to spinal nerve (K(trans) 3.8±1.5 10(-3)/min vs. 1.6±0.9 10(-3)/min, p-value: <0.001) combined with an increased interstitial leakage of contrast agent into the extravascular-extracellular-space (Ve 38.1±19.2% vs. 17.3±9.9%, p-value: <0.001). Parameters showed no statistically significant difference on DRG-level (L5 vs. S1; p-value: 0.62 (K(trans)); 0.17 (Ve)) and -side (left vs. right; p-value: 0.25 (K(trans)); 0.79 (Ve)). Female gender was associated with a significantly increased permeability (K(trans) female 4.3±1.4 10(-3)/min vs. male 3.4±0.9 10(-3)/min, p-value: <0.05) but no statistically significant differences in interstitial leakage (Ve female 40.1±14,1% vs. male 34.5±17.4%, p-value: 0.24). DRG showed distinct spatial distribution patterns of perfusion: K(trans) and Ve were significantly higher in the CBRA than in the NFRA (K(trans) 4.4±1.8 10(-3)/min vs. 1.7±1.2 10(-3)/min, p-value: <0.001 and Ve 40.9±21.3% vs. 15.1±11.7%, p-value: <0.001). CONCLUSION: Non-invasive and in-vivo measurement of human DRG perfusion by MRI is a feasible technique. DRG show substantially higher permeability and interstitial leakage than spinal nerves. Even distinct physiological perfusion patterns for different microstructural compartments could be observed within the DRG. The technique may become particularly useful for future research on the poorly understood human sensory neuropathies and pain syndromes.

Magnetic resonance neurography detects diabetic neuropathy early and with Proximal Predominance.

OBJECTIVE: The aim of this work was to localize and quantify alterations of nerve microstructure in diabetic polyneuropathy (DPN) by magnetic resonance (MR) neurography with large anatomical coverage. METHODS: Patients (N = 25) with mild-to-moderate (Neuropathy-Symptom-Score [NSS]/Neuropathy Deficit Score [NDS] 3.8 ± 0.3/2.6 ± 0.5) and patients (n = 10) with severe DPN (6.2 ± 0.6/7.4 ± 0.5) were compared to patients (n = 15) with diabetes but no DPN and to age-/sex-matched nondiabetic controls (n = 25). All subjects underwent MR neurography with large spatial coverage and high resolution from spinal nerve to ankle level: four slabs per leg, each with 35 axial slices (T2- and proton-density-weighted two dimensional turbo-spin-echo sequences; voxel size: 0.4 × 0.3 × 3.5 mm(3) ) and a three-dimensional T2-weighted sequence to cover spinal nerves and plexus. Nerve segmentation was performed on a total of 280 slices per subject. Nerve lesion voxels were determined independently from operator input by statistical classification against the nondiabetic cohort. At the site with highest lesion-voxel burden, signal quantification was performed by calculating nerve proton spin density and T2 relaxation time. RESULTS: Total burden of nerve lesion voxels was significantly increased in DPN (p = 0.003) with strong spatial predominance at thigh level, where average lesion voxel load was significantly higher in severe (57 ± 18.4; p = 0.0022) and in mild-to-moderate DPN (35 ± 4.0; p < 0.001) than in controls (18 ± 3.6). Signal quantification at the site of predominant lesion burden (thigh) revealed a significant increase of nerve proton spin density in severe (360 ± 22.9; p = 0.043) and in mild-to-moderate DPN (365 ± 15.2; p = 0.001) versus controls (288 ± 13.4), but not of T2 relaxation time (p = 0.49). Nerve proton spin density predicted severity of DPN with an odds ratio of 2.9 (95% confidence interval: 2.4-3.5; p < 0.001) per 100 proton spins. INTERPRETATION: In DPN, the predominant site of microstructural nerve alteration is at the thigh level with a strong proximal-to-distal gradient. Nerve proton spin density at the thigh level is a novel quantitative imaging biomarker of early DPN and increases with neuropathy severity.

Prognostic value of combined visualization of MR diffusion and perfusion maps in glioblastoma.

We analyzed whether the combined visualization of decreased apparent diffusion coefficient (ADC) values and increased cerebral blood volume (CBV) in perfusion imaging can identify prognosis-related growth patterns in patients with newly diagnosed glioblastoma. Sixty-five consecutive patients were examined with diffusion and dynamic susceptibility-weighted contrast-enhanced perfusion weighted MRI. ADC and CBV maps were co-registered on the T1-w image and a region of interest (ROI) was manually delineated encompassing the enhancing lesion. Within this ROI pixels with ADC values the 70th percentile (CBVmax) and the intersection of pixels with ADCmin and CBVmax were automatically calculated and visualized. Initially, all tumors with a mean intersection greater than the upper quartile of the normally distributed mean intersection of all patients were subsumed to the first growth pattern termed big intersection (BI). Subsequently, the remaining tumors' growth patterns were categorized depending on the qualitative representation of ADCmin, CBVmax and their intersection. Log-rank test exposed a significantly longer overall survival of BI (n = 16) compared to non-BI group (n = 49) (p = 0.0057). Thirty-one, four and 14 patients of the non-BI group were classified as predominant ADC-, CBV- and mixed growth group, respectively. In a multivariate Cox regression model, the BI-, CBV- and mixed groups had significantly lower adjusted hazard ratios (p-value, α(Bonferroni) < 0.006) when compared to the reference group ADC: 0.29 (0.0027), 0.11 (0.038) and 0.33 (0.0059). Our study provides evidence that the combination of diffusion and perfusion imaging allows visualization of different glioblastoma growth patterns that are associated with prognosis. A possible biological hypothesis for this finding could be the interpretation of the ADCmin fraction as the invasion-front of tumor cells while the CBVmax fraction might represent the vascular rich tumor border that is "trailing behind" the invasion-front in the ADC group.

Diagnostic signs of motor neuropathy in MR neurography: nerve lesions and muscle denervation.

OBJECTIVE: To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). METHODS: Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. RESULTS: All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. CONCLUSIONS: MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. KEY POINTS: • In peripheral neuropathy, T2-w nerve lesions are more frequent than muscle denervation. • Muscle denervation almost never occurs without detectable lesions in corresponding nerves. • MRN-aided diagnosis of peripheral motor neuropathy should focus primarily on nerve lesions. • Increased muscular T2-w signal intensity without concomitant nerve lesions indicates other aetiology.

Peripheral neuropathy: detection with diffusion-tensor imaging.

PURPOSE: To investigate the ability of diffusion-tensor imaging (DTI) and T2 to help detect the mildest nerve lesion conceivable, that is, subclinical ulnar neuropathy at the elbow. MATERIALS AND METHODS: This prospective study was approved by the institutional ethics board. Written informed consent was obtained from all participants. Magnetic resonance neurography was performed at 3.0 T by using proton density- and T2-weighted relaxometry and DTI on elbows in 30 healthy subjects without clinical evidence of neuropathy. Quantitative analysis of ulnar nerve T2 and fractional anisotropy (FA) was performed, and T2 and FA values were correlated to electrical nerve conduction velocities (NCVs) with Pearson correlation analysis. Additional qualitative assessment of T2-weighted and FA images was performed by two readers, and sensitivity and specificity were calculated. RESULTS: Ten of the 30 subjects (33%) had NCV slowing across the elbow segment. Compared with subjects without NCV slowing, subjects with slowing had decreased FA values (0.51 ± 0.09 vs 0.41 ± 0.07, respectively; P = .006) and increased T2 values (64.2 msec ± 10.9 vs 76.2 msec ± 13.7, respectively; P = .01) in the proximal ulnar sulcus. FA values showed a significant correlation (P = .01) with NCV slowing over the sulcus as an electrophysiologic indicator of myelin sheath damage. Qualitative assessment of FA maps and T2-weighted images helped identify subjects with conduction slowing with a sensitivity of 80% and 55%, respectively, and a specificity of 83% and 63%. CONCLUSION: FA maps can accurately depict even mild peripheral neuropathy and perform better than the current standard of reference, T2-weighted images. DTI may therefore add diagnostic value as a highly sensitive technique for the detection of peripheral neuropathy.

Infiltrative patterns of glioblastoma: Identification of tumor progress using apparent diffusion coefficient histograms.

PURPOSE: To investigate whether apparent diffusion coefficient (ADC) histogram analysis can differentiate between patients presenting T2-progress and patients presenting stable T2-signal in glioblastoma. MATERIALS AND METHODS: Fourteen patients presenting an isolated T2-progress and a matched control group exhibiting stable disease were included. Relative ADC value distribution within tumoral and peritumoral FLAIR hyperintensities were evaluated using ADC-histogram analysis. Severity and frequency of ADC shift between baseline, T2-progress, and subsequent T1-progress were analyzed using the Wilcoxon test. RESULTS: The shift of ADC histograms either to higher or to lower values in case of T2-progress was significantly more severe than in the control group (P value 0.05). Furthermore, a significant shift toward lower ADC values (P value 0.02) was detected when comparing ADC histograms of patients with T2-progress and subsequent T1-progress. CONCLUSION: The basis for the observed ADC shift in isolated T2-progress may be time dependent: Initially, formation of peritumoral edema may cause an increase of ADC values that is followed by tumor cells infiltrating the surrounding tissue, causing a subsequent decrease of ADC values. The shift toward lower ADC values in case of subsequent T1-progress confirms this hypothesis and provides further evidence for T2-progress being an intermediate step between stable disease (SD) and T1-progress.

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.

Magnetization Transfer Ratio of Peripheral Nerve and Skeletal Muscle : Correlation with Demographic Variables in Healthy Volunteers.

PURPOSE: To assess the correlation of peripheral nerve and skeletal muscle magnetization transfer ratio (MTR) with demographic variables. METHODS: In this study 59 healthy adults evenly distributed across 6 decades (mean age 50.5 years ±17.1, 29 women) underwent magnetization transfer imaging and high-resolution T2-weighted imaging of the sciatic nerve at 3 T. Mean sciatic nerve MTR as well as MTR of biceps femoris and vastus lateralis muscles were calculated based on manual segmentation on six representative slices. Correlations of MTR with age, body height, body weight, and body mass index (BMI) were expressed by Pearson coefficients. Best predictors for nerve and muscle MTR were determined using a multiple linear regression model with forward variable selection and fivefold cross-validation. RESULTS: Sciatic nerve MTR showed significant negative correlations with age (r = -0.47, p < 0.001), BMI (r = -0.44, p < 0.001), and body weight (r = -0.36, p = 0.006) but not with body height (p = 0.55). The multiple linear regression model determined age and BMI as best predictors for nerve MTR (R2 = 0.40). The MTR values were different between nerve and muscle tissue (p < 0.0001), but similar between muscles. Muscle MTR was associated with BMI (r = -0.46, p < 0.001 and r = -0.40, p = 0.002) and body weight (r = -0.36, p = 0.005 and r = -0.28, p = 0.035). The BMI was selected as best predictor for mean muscle MTR in the multiple linear regression model (R2 = 0.26). CONCLUSION: Peripheral nerve MTR decreases with higher age and BMI. Studies that assess peripheral nerve MTR should consider age and BMI effects. Skeletal muscle MTR is primarily associated with BMI but overall less dependent on demographic variables.

Spatial Distribution and Long-Term Alterations of Peripheral Nerve Lesions in Schwannomatosis.

Purpose To examine the spatial distribution and long-term alterations of peripheral nerve lesions in patients with schwannomatosis by in vivo high-resolution magnetic resonance neurography (MRN). Methods In this prospective study, the lumbosacral plexus as well as the right sciatic, tibial, and peroneal nerves were examined in 15 patients diagnosed with schwannomatosis by a standardized MRN protocol at 3 Tesla. Micro-, intermediate- and macrolesions were assessed according to their number, diameter and spatial distribution. Moreover, in nine patients, peripheral nerve lesions were compared to follow-up examinations after 39 to 71 months. Results In comparison to intermediate and macrolesions, microlesions were the predominant lesion entity at the level of the proximal (p < 0.001), mid- (p < 0.001), and distal thigh (p < 0.01). Compared to the proximal calf level, the lesion number was increased at the proximal (p < 0.05), mid- (p < 0.01), and distal thigh level (p < 0.01), while between the different thigh levels, no differences in lesion numbers were found. In the follow-up examinations, the lesion number was unchanged for micro-, intermediate and macrolesions. The diameter of lesions in the follow-up examination was decreased for microlesions (p < 0.01), not different for intermediate lesions, and increased for macrolesions (p < 0.01). Conclusion Microlesions represent the predominant type of peripheral nerve lesion in schwannomatosis and show a rather consistent distribution pattern in long-term follow-up. In contrast to the accumulation of nerve lesions, primarily in the distal nerve segments in NF2, the lesion numbers in schwannomatosis peak at the mid-thigh level. Towards more distal portions, the lesion number markedly decreases, which is considered as a general feature of other types of small fiber neuropathy.

Dorsal Root Ganglia Volume-Normative Values, Correlation with Demographic Determinants and Reliability of Three Different Methods of Volumetry.

Background: Dorsal root ganglia (DRG) volume assessment by MR-Neurography (MRN) has evolved to an important imaging marker in the diagnostic workup of various peripheral neuropathies and pain syndromes. The aim of this study was (1) to assess normal values of DRG volume and correlations with demographic determinants and (2) to quantify the inter-reader and inter-method reliability of three different methods of DRG volumetry. Methods: Sixty healthy subjects (mean age: 59.1, range 23-79) were examined using a 3D T2-weighted MRN of the lumbosacral plexus at 3 Tesla. Normal values of DRG L3 to S2 were obtained after exact volumetry based on manual 3D segmentation and correlations with demographic variables were assessed. For the assessment of inter-reader and inter-method reliability, DRG volumes in a subset of 25 participants were measured by two independent readers, each applying (1) exact volumetry based on 3D segmentation, (2) axis-corrected, and (3) non-axis-corrected volume estimation. Intraclass correlation coefficients were reported and the Bland-Altman analysis was conducted. Results: Mean DRG volumes ranged from 124.8 mm3 for L3 to 323.3 mm3 for S1 and did not differ between right and left DRG. DRG volume (mean of L3 to S1) correlated with body height (r = 0.42; p = 0.0008) and weight (r = 0.34; p = 0.0087). DRG of men were larger than of women (p = 0.0002); however, no difference remained after correction for body height. Inter-reader reliability was high for all three methods but best for exact volumetry (ICC = 0.99). While axis-corrected estimation was not associated with a relevant bias, non-axis-corrected estimation systematically overestimated DRG volume by on average of 15.55 mm3 (reader 1) or 18.00 mm3 (reader 2) when compared with exact volumetry. Conclusion: The here presented normal values of lumbosacral DRG volume and the correlations with height and weight may be considered in future disease specific studies and possible clinical applications. Exact volumetry was most reliable and should be considered the gold standard. However, the reliability of axis-corrected and non-axis-corrected volume estimation was also high and might still be sufficient, depending on the degree of the required measurement accuracy.

Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment : Longitudinal Assessment by Computed Tomography.

PURPOSE: Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose. METHODS: For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1-t4) with the following median and ranges in months: 3.1 (0.4-4.9), 6.2 (5.3-7.8), 10.4 (8.2-11.9), and 18.4 (12.8-49.8). RESULTS: DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p < 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p < 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08). CONCLUSION: CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker.