Magnetic resonance neurography in spinal cord injury: Imaging findings and clinical significance.

BACKGROUND AND PURPOSE: It is unknown whether changes to the peripheral nervous system following spinal cord injury (SCI) are relevant for functional recovery or the development of neuropathic pain below the level of injury. Magnetic resonance neurography (MRN) at 3 T allows detection and localization of structural and functional nerve damage. This study aimed to combine MRN and clinical assessments in individuals with chronic SCI and nondisabled controls. METHODS: Twenty participants with chronic SCI and 20 controls matched for gender, age, and body mass index underwent MRN of the L5 dorsal root ganglia (DRG) and the sciatic nerve. DRG volume, sciatic nerve mean cross-sectional area (CSA), fascicular lesion load, and fractional anisotropy (FA), a marker for functional nerve integrity, were calculated. Results were correlated with clinical assessments and nerve conduction studies. RESULTS: Sciatic nerve CSA and lesion load were higher (21.29 ± 5.82 mm2 vs. 14.08 ± 4.62 mm2 , p < 0.001; and 8.70 ± 7.47% vs. 3.60 ± 2.45%, p < 0.001) in individuals with SCI compared to controls, whereas FA was lower (0.55 ± 0.11 vs. 0.63 ± 0.08, p = 0.022). DRG volumes were larger in individuals with SCI who suffered from neuropathic pain compared to those without neuropathic pain (223.7 ± 53.08 mm3 vs. 159.7 ± 55.66 mm3 , p = 0.043). Sciatic MRN parameters correlated with electrophysiological results but did not correlate with the extent of myelopathy or clinical severity of SCI. CONCLUSIONS: Individuals with chronic SCI are subject to a decline of structural peripheral nerve integrity that may occur independently from the clinical severity of SCI. Larger volumes of DRG in SCI with neuropathic pain support existing evidence from animal studies on SCI-related neuropathic pain.

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.

Structural Nerve Remodeling at 3-T MR Neurography Differs between Painful and Painless Diabetic Polyneuropathy in Type 1 or 2 Diabetes.

Background The pathophysiologic mechanisms underlying painful symptoms in diabetic polyneuropathy (DPN) are poorly understood. They may be associated with MRI characteristics, which have not yet been investigated. Purpose To investigate correlations between nerve structure, load and spatial distribution of nerve lesions, and pain in patients with DPN. Materials and Methods In this prospective single-center cross-sectional study, participants with type 1 or 2 diabetes volunteered between June 2015 and March 2018. Participants underwent 3-T MR neurography of the sciatic nerve with a T2-weighed fat-suppressed sequence, which was preceded by clinical and electrophysiologic tests. For group comparisons, analysis of variance or the Kruskal-Wallis test was performed depending on Gaussian or non-Gaussian distribution of data. Spearman correlation coefficients were calculated for correlation analysis. Results A total of 131 participants (mean age, 62 years ± 11 [standard deviation]; 82 men) with either type 1 (n = 45) or type 2 (n = 86) diabetes were evaluated with painful (n = 64), painless (n = 37), or no (n = 30) DPN. Participants who had painful diabetic neuropathy had a higher percentage of nerve lesions in the full nerve volume (15.2% ± 1.6) than did participants with nonpainful DPN (10.4% ± 1.7, P = .03) or no DPN (8.3% ± 1.7; P < .001). The amount and extension of T2-weighted hyperintense nerve lesions correlated positively with the neuropathy disability score (r = 0.37; 95% confidence interval [CI]: 0.21, 0.52; r = 0.37; 95% CI: 0.20, 0.52, respectively) and the neuropathy symptom score (r = 0.41; 95% CI: 0.25, 0.55; r = 0.34; 95% CI: 0.17, 0.49, respectively). Negative correlations were found for the tibial nerve conduction velocity (r = -0.23; 95% CI: -0.44, -0.01; r = -0.37; 95% CI: -0.55, -0.15, respectively). The cross-sectional area of the nerve was positively correlated with the neuropathy disability score (r = 0.23; 95% CI: 0.03, 0.36). Negative correlations were found for the tibial nerve conduction velocity (r = -0.24; 95% CI: -0.45, -0.01). Conclusion The amount and extension of T2-weighted hyperintense fascicular nerve lesions were greater in patients with painful diabetic neuropathy than in those with painless diabetic neuropathy. These results suggest that proximal fascicular damage is associated with the evolution of painful sensory symptoms in diabetic polyneuropathy. © RSNA, 2019 Online supplemental material is available for this article.

Quantitative magnetic resonance neurography in chronic inflammatory demyelinating polyradiculoneuropathy: A longitudinal study over 6 years.

OBJECTIVE: To evaluate magnetic resonance neurography (MRN) for the longitudinal assessment of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Prospective examination of twelve CIDP patients by neurological assessment, MRN, and nerve conduction studies in 2016 and 6 years later in 2022. Imaging parameters were compared with matched healthy controls and correlated with clinical and electrophysiological markers. The MRN protocol included T2-weighted imaging, diffusion tensor imaging (DTI), T2 relaxometry, and magnetization transfer imaging (MTI). RESULTS: Nerve cross-sectional area (CSA) was increased in CIDP patients compared to controls (plexus: p = 0.003; sciatic nerve: p < 0.001). Over 6 years, nerve CSA decreased in CIDP patients, most pronounced at the lumbosacral plexus (p = 0.015). Longitudinally, changes in CSA correlated with changes in the inflammatory neuropathy cause and treatment validated overall disability sum score (INCAT/ODSS) (p = 0.006). High initial nerve CSA was inversely correlated with changes in the INCAT/ODSS over 6 years (p < 0.05). The DTI parameter fractional anisotropy (FA) showed robust correlations with electrodiagnostic testing both cross-sectionally and longitudinally (p < 0.05). MTI as a newly added imaging technique revealed a significantly reduced magnetization transfer ratio (MTR) in CIDP patients (p < 0.01), suggesting underlying changes in macromolecular tissue composition, and correlated significantly with electrophysiological parameters of demyelination (p < 0.05). INTERPRETATION: This study provides evidence that changes in nerve CSA and FA reflect the clinical and electrophysiological course of CIDP patients. Initial nerve hypertrophy might predict a rather benign course or better therapy response.

Inferior long-term Results of a Prospective Randomized Controlled Trial initially demonstrating enhanced Sensory Nerve Recovery using a Chitosan Nerve Tube.

INTRODUCTION: Traumatic peripheral nerve injuries can result in significant functional impairments and long-term sequelae. This study evaluated the long-term outcomes of a chitosan tube implantation protecting the epineural coaptation after peripheral nerve injuries using two different tube versions (V 1.0 and V 2.0 with different wall thickness and resorption characteristics) compared to a control group. The study focused on pain levels, sensory function, and overall functional outcomes. METHODS: Patients who received tube implantation around direct coaptation sites of digital nerves were prospectively randomized and compared to control patients without additional tube protection. Pain levels, sensory function, grip force, and functional scores were assessed at different time points, ranging from three months to five years after the procedure. Furthermore, biodegradation of the tubes was measured via high-resolution MR-neurography (MRN) and categorized. RESULTS: Long-term evaluation revealed that patients with V 1.0 had higher pain levels compared to the control group after five years. They also reported more symptoms of numbness and hypersensitivity. V 2.0 patients exhibited higher pain levels at three months, which did not persist at six months. However, they showed compromised sensory function, with higher values of two-point discrimination compared to V 1.0 and the control group. No differences were found in grip force or functional scores between the groups. MRI displayed remnants of implants even in long-term follow-up. DISCUSSION: The findings suggest potential limitations due to pain increase and impaired sensory function associated with tube implantation in the long term. However, in the short term, the material seemed to have a protective effect (as published previously). The resorption process was not completed at the end of the observation period of five years. This might explain the prolonged scarring and inferior long-term results. Future research should focus on improving tube materials and design to minimize adverse effects and enhance functional outcomes in patients with peripheral nerve injuries.

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.

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.

Simultaneous Multislice Accelerated TSE for Improved Spatiotemporal Resolution and Diagnostic Accuracy in Magnetic Resonance Neurography: A Feasibility Study.

OBJECTIVES: This study aims to evaluate the utility of simultaneous multislice (SMS) acceleration for routine magnetic resonance neurography (MRN) at 3 T. MATERIALS AND METHODS: Patients with multiple sclerosis underwent MRN of the sciatic nerve consisting of a standard fat-saturated T2-weighted turbo spin echo (TSE) sequence using integrated parallel acquisition technique (PAT2) acceleration and 2 T2 TSE sequences using a combination of PAT-SMS acceleration (1) to reduce scan time (PAT2-SMS2; SMS-TSE FAST ) and (2) for time neutral increase of in-plane resolution (PAT1-SMS2; SMS-TSE HR ). Acquisition times were 5:29 minutes for the standard T2 TSE, 3:12 minutes for the SMS-TSE FAST , and 5:24 minutes for the SMS-TSE HR . Six qualitative imaging parameters were analyzed by 2 blinded readers using a 5-point Likert scale and T2 nerve lesions were quantified, respectively. Qualitative and quantitative image parameters were compared, and both interrater and intrarater reproducibility were statistically assessed. In addition, signal-to-noise ratio/contrast-to-noise ratio (CNR) was obtained in healthy controls using the exact same imaging protocol. RESULTS: A total of 15 patients with MS (mean age ± standard deviation, 38.1 ± 11 years) and 10 healthy controls (mean age, 29.1 ± 7 years) were enrolled in this study. CNR analysis was highly reliable (intraclass correlation coefficient, 0.755-0.948) and revealed a significant CNR decrease for the sciatic nerve for both SMS protocols compared with standard T2 TSE (SMS-TSE FAST /SMS-TSE HR , -39%/-55%; P ≤ 0.01). Intrarater and interrater reliability of qualitative image review was good to excellent (κ: 0.672-0.971/0.617-0.883). Compared with the standard T2 TSE sequence, both SMS methods were shown to be superior in reducing pulsatile flow artifacts ( P < 0.01). Ratings for muscle border sharpness, detailed muscle structures, nerve border sharpness, and nerve fascicular structure did not differ significantly between the standard T2 TSE and the SMS-TSE FAST ( P > 0.05) and were significantly better for the SMS-TSE HR than for standard T2 TSE ( P < 0.001). Muscle signal homogeneity was mildly inferior for both SMS-TSE FAST ( P > 0.05) and SMS-TSE HR ( P < 0.001). A significantly higher number of T2 nerve lesions were detected by SMS-TSE HR ( P ≤ 0.01) compared with the standard T2 TSE and SMS-TSE FAST , whereas no significant difference was observed between the standard T2 TSE and SMS-TSE FAST . CONCLUSIONS: Implementation of SMS offers either to substantially reduce acquisition time by over 40% without significantly impeding image quality compared with the standard T2 TSE or to increase in-plane resolution for a high-resolution approach and improved depiction of T2 nerve lesions while keeping acquisition times constant. This addresses the specific needs of MRN by providing different imaging approaches for 2D clinical MRN.

MR microscopy to assess clot composition following mechanical thrombectomy predicts recanalization and clinical outcome.

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for patients with a stroke and large vessel occlusion. Clot composition is not routinely assessed in clinical practice as no specific diagnostic value is attributed to it, and MT is performed in a standardized 'non-personalized' approach. Whether different clot compositions are associated with intrinsic likelihoods of recanalization success or treatment outcome is unknown. METHODS: We performed a prospective, non-randomized, single-center study and analyzed the clot composition in 60 consecutive patients with ischemic stroke undergoing MT. Clots were assessed by ex vivo multiparametric MRI at 9.4 T (MR microscopy), cone beam CT, and histopathology. Clot imaging was correlated with preinterventional CT and clinical data. RESULTS: MR microscopy showed red blood cell (RBC)-rich (21.7%), platelet-rich (white,38.3%) or mixed clots (40.0%) as distinct morphological entities, and MR microscopy had high accuracy of 95.4% to differentiate clots. Clot composition could be further stratified on preinterventional non-contrast head CT by quantification of the hyperdense artery sign. During MT, white clots required more passes to achieve final recanalization and were not amenable to contact aspiration compared with mixed and RBC-rich clots (maneuvers: 4.7 vs 3.1 and 1.2 passes, P<0.05 and P<0.001, respectively), whereas RBC-rich clots showed higher probability of first pass recanalization (76.9%) compared with white clots (17.4%). White clots were associated with poorer clinical outcome at discharge and 90 days after MT. CONCLUSION: Our study introduces MR microscopy to show that the hyperdense artery sign or MR relaxometry could guide interventional strategy. This could enable a personalized treatment approach to improve outcome of patients undergoing MT.

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.

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.

Reliability and validity of a standardised ultrasound examination protocol to quantify vastus lateralis muscle.

OBJECTIVE: To evaluate the reliability and validity of a standardized ultrasound examination protocol for measuring vastus lateralis muscle size. DESIGN: Prospective cohort study. SUBJECTS: Sixteen staff members of the university hospital of Heidelberg. METHODS: Muscle thickness, cross-sectional area and subcutaneous adipose tissue thickness were measured at 3 standardized sites on the right and left vastus lateralis muscle. Ultrasound measurements were collected by 2 independent investigators on 2 different days and compared with magnetic resonance imaging measurements. RESULTS: Intraclass correlation coefficients (ICC) for intra- and inter-rater reliability showed very good closeness of agreement for all parameters (ICC = 0.929-0.994, p < 0.001). Muscle thickness and subcutaneous adipose tissue thickness ultrasound and magnetic resonance imaging measurements revealed good to very good closeness of agreement (ICC = 0.835-0.969, p < 0.001), whereas cross-sectional area showed only average closeness of agreement (ICC = 0.727, p < 0.001). A strong predictive positive correlation for ultrasound and magnetic resonance imaging-based measurements of cross-sectional area was found (R² = 0.793, p < 0.001). CONCLUSION: By standardization of an examination protocol, quantitative vastus lateralis muscle ultrasound proved to be a reliable method for assessing vastus lateralis muscle size. Furthermore, this protocol is valid for measuring muscle thickness and subcutaneous adipose tissue thickness, although there seems to be a systematic underestimation of cross-sectional area depending on subcutaneous adipose tissue thickness.

In Vivo Visualization of Tissue Damage Induced by Percutaneous Muscle Biopsy via Novel High-Resolution MR Imaging.

PURPOSE: Percutaneous muscle biopsy is the gold standard for tissue assessment in clinical practice and scientific studies. The aim of this study was to assess and quantify the ensuing tissue damage by in vivo magnetic resonance imaging (MRI). METHODS: In this prospective study, we enrolled 22 healthy participants who underwent MRI of the thigh musculature about 1 wk after a percutaneous muscle biopsy of the vastus lateralis muscle. A total of 17 participants also volunteered for a second MR examination 2 wk after biopsy. Volumes of susceptibility-weighted imaging (SWI) lesions and muscle edema were assessed by SWI and T2-weighted MRI, respectively, after manual segmentation by two independent readers. For quantitative in vivo hematoma volume assessment, we additionally determined signal changes induced by experimental hematoma in an ex vivo model. RESULTS: Mean overall volume of SWI lesions 1 wk after biopsy was 26.5 ± 21.7 µL, accompanied by a mean perifocal edema volume of 790.1 ± 591.4 µL. In participants who underwent two examinations, mean volume of SWI lesions slightly decreased from 29.8 ± 23.6 to 23.9 ± 16.8 µL within 1 wk (P = 0.13). Muscle edema volume decreased from 820.2 ± 632.4 to 359.6 ± 207.3 µL at the same time (P = 0.006). By calibration with the ex vivo findings, signal alterations on SWI corresponded to a blood volume of approximately 10-50 µL. CONCLUSIONS: Intramuscular hematoma and accompanying muscle edema after percutaneous biopsy are small and decrease rapidly within the first 2 wk. These in vivo findings underline the limited invasiveness of the procedure.

Peripheral Nerve Diffusion Tensor Imaging : Interreader and Test-retest Reliability as Quantified by the Standard Error of Measurement.

PURPOSE: Diffusion tensor imaging (DTI) is increasingly being used in magnetic resonance neurography (MRN). The purpose of this study was to determine the interreader and test-retest reliability of peripheral nerve DTI in MRN with focus on the sciatic nerve. METHODS: In this prospective study 27 healthy volunteers each underwent 3 scans of a short DTI protocol on separate days consisting of a T2-weighted turbo spin-echo and single-shot DTI sequence of the sciatic nerve of the dominant leg. The DTI parameters fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were obtained after manual nerve segmentation by two independent readers. Intraclass correlation coefficients (ICC), standard error of measurement (SEM), and Bland-Altman plots were calculated as measures for both interreader and test-retest agreement for all readout parameters. RESULTS: The mean ± standard deviation was 0.507 ± 0.05 for FA, 1308.5 ± 162.4â€¯× 10-6 mm2/s for MD, 905.6 ± 145.4 ×10-6 mm2/s for RD and 2114.1 ± 219.2â€¯× 10-6 mm2/s for AD. The SEM for FA was 0.02 for interreader and test-retest agreement, the SEM for MD, RD, and AD ranged between 46.2â€¯× 10-6 mm2/s (RD) and 70.1â€¯× 10-6 mm2/s (AD) for interreader reliability and between 45.9â€¯× 10-6 mm2/s (RD) and 70.1â€¯× 10-6 mm2/s (AD) for test-retest reliability. The ICC for interreader reliability of DTI parameters ranged between 0.81 and 0.92 and ICC for test-retest reliability between 0.76 and 0.91. CONCLUSION: Peripheral nerve DTI of the sciatic nerve is reliable and reproducible. The measures presented here may serve as first orientation values of measurement accuracy when interpreting parameters of sciatic nerve DTI.

Aortic arch replacement with frozen elephant trunk technique - a single-center study.

BACKGROUND: The frozen elephant trunk (FET) technique was developed to facilitate the two-stage surgery of extensive pathologies of the thoracic aorta and is now routinely applied in acute and chronic aortic syndromes. METHODS: From 11/2006 to 07/2017, 68 patients underwent aortic arch repair using the FET technique. Patients received either the Jotec E-vita Open graft (n = 57) or the Vascutek Thoraflex hybrid prosthesis (n = 11). Both, group 1 (acute aortic dissection type A and B; symptomatic penetrating aortic ulcer) and group 2 (aortic aneurysm; chronic aortic dissection) included 34 patients each. RESULTS: Early mortality was 13.2% (14.7% in group 1 vs. 11.7% in group 2, p = 0.720). Neurological complications occurred in 12 patients (17.6%) (stroke: 8.8 vs. 11.7%; p = 0.797 and spinal cord injury: 8.8 vs. 5.9%; p = 0.642 in groups 1 vs. 2 respectively). Cardiopulmonary bypass time and cross clamp time were significantly longer in group 1 (252.2 ± 73.5 and 148.3 ± 34 min vs. 189.2 ± 47.8 and 116.3 ± 34.5 min; p <  0.001). The overall 1-, 3- and 7-year-survival was 80.9, 80.9 and 74.2% with no significant differences between groups 1 and 2. Expansion of true lumen after FET implantation was significant at all levels in both groups for patients with aortic dissection. One-, 3-, and 7-year-freedom from secondary (re-)intervention for patients for aortic dissection was 96.9, 90.2 and 82.7% with no significant differences between groups 1 and 2; p = 0.575. CONCLUSION: The FET technique can be applied in acute aortic syndromes with similar risks regarding adverse events or mortality when compared to chronic degenerative aortic disease. Postoperative increase in true lumen diameter mirrors decrease of false lumen diameter, goes along with favorable midterm outcome and prolongs freedom from secondary interventions in acute aortic dissection.

Association of Serum Cholesterol Levels With Peripheral Nerve Damage in Patients With Type 2 Diabetes.

Importance: Lowering serum cholesterol levels is a well-established treatment for dyslipidemia in patients with type 2 diabetes (T2D). However, nerve lesions in patients with T2D increase with lower serum cholesterol levels, suggesting that lowering serum cholesterol levels is associated with diabetic polyneuropathy (DPN) in patients with T2D. Objective: To investigate whether there is an association between serum cholesterol levels and peripheral nerve lesions in patients with T2D with and without DPN. Design, Setting, and Participants: This single-center, cross-sectional, prospective cohort study was performed from June 1, 2015, to March 31, 2018. Observers were blinded to clinical data. A total of 256 participants were approached, of whom 156 were excluded. A total of 100 participants consented to undergo magnetic resonance neurography of the right leg at the Department of Neuroradiology and clinical, serologic, and electrophysiologic assessment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. Exposures: Quantification of the nerve's diameter and lipid equivalent lesion (LEL) load with a subsequent analysis of all acquired clinical and serologic data with use of 3.0-T magnetic resonance neurography of the right leg with 3-dimensional reconstruction of the sciatic nerve. Main Outcomes and Measures: The primary outcome was lesion load and extension. Secondary outcomes were clinical, serologic, and electrophysiologic findings. Results: A total of 100 participants with T2D (mean [SD] age, 64.6 [0.9] years; 68 [68.0%] male) participated in the study. The LEL load correlated positively with the nerve's mean cross-sectional area (r = 0.44; P < .001) and the maximum length of a lesion (r = 0.71; P < .001). The LEL load was negatively associated with total serum cholesterol level (r = -0.41; P < .001), high-density lipoprotein cholesterol level (r = -0.30; P = .006), low-density lipoprotein cholesterol level (r = -0.33; P = .003), nerve conduction velocities of the tibial (r = -0.33; P = .01) and peroneal (r = -0.51; P < .001) nerves, and nerve conduction amplitudes of the tibial (r = -0.31; P = .02) and peroneal (r = -0.28; P = .03) nerves. Conclusions and Relevance: The findings suggest that lowering serum cholesterol levels in patients with T2D and DPN is associated with a higher amount of nerve lesions and declining nerve conduction velocities and amplitudes. These findings may be relevant to emerging therapies that promote an aggressive lowering of serum cholesterol levels in patients with T2D.

Impact of Human Adipose Tissue-Derived Stem Cells on Malignant Melanoma Cells in An In Vitro Co-culture Model.

This study focuses on the interactions of human adipose tissue-derived stem cells (ADSCs) and malignant melanoma cells (MMCs) with regard to future cell-based skin therapies. The aim was to identify potential oncological risks as ADSCs could unintentionally be sited within the proximity of the tumor microenvironment of MMCs. An indirect co-culture model was used to analyze interactions between ADSCs and four different established melanoma cell lines (G-361, SK-Mel-5, MeWo and A2058) as well as two low-passage primary melanoma cell cultures (M1 and M2). Doubling time, migration and invasion, angiogenesis, quantitative real-time PCR of 229 tumor-associated genes and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPs) were evaluated. Co-culture with ADSCs significantly increased migration capacity of G-361, SK-Mel-5, A2058, MeWo and M1 and invasion capacity of G-361, SK-Mel-5 and A2058 melanoma cells. Furthermore, conditioned media from all ADSC-MMC-co-cultures induced tube formation in an angiogenesis assay in vitro. Gene expression analysis of ADSCs and MMCs, especially of low-passage melanoma cell cultures, revealed an increased expression of various genes with tumor-promoting activities, such as CXCL12, PTGS2, IL-6, and HGF upon ADSC-MMC-co-culture. In this context, a significant increase (up to 5,145-fold) in the expression of numerous tumor-associated proteins could be observed, e.g. several pro-angiogenic factors, such as VEGF, IL-8, and CCL2, as well as different matrix metalloproteinases, especially MMP-2. In conclusion, the current report clearly demonstrates that a bi-directional crosstalk between ADSCs and melanoma cells can enhance different malignant properties of melanoma cells in vitro.

Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications.

INTRODUCTION: This is the first study evaluating the interactions of human adipose tissue derived stem cells (ADSCs) and human squamous cell carcinoma cells (SCCs), with regard to a prospective cell-based skin regenerative therapy and a thereby unintended co-localization of ADSCs and SCCs. METHODS: ADSCs were co-cultured with A431-SCCs and primary SCCs (pSCCs) in a transwell system, and cell-cell interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real time PCR of 229 tumor associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPS). Results of co-culture were compared to those of the respective mono-culture. RESULTS: ADSCs' proliferation on the plate was significantly increased when co-cultured with A431-SCCs (P = 0.038). PSCCs and ADSCs significantly decreased their proliferation in co-culture if cultured on the plate (P <0.001 and P = 0.03). The migration of pSCC was significantly increased in co-culture (P = 0.009), as well as that of ADSCs in A431-SCC-co-culture (P = 0.012). The invasive behavior of pSCCs and A431-SCCs was significantly increased in co-culture by a mean of 33% and 35%, respectively (P = 0.038 and P <0.001). Furthermore, conditioned media from co-cultured ADSC-A431-SCCs and co-cultured ADSCs-pSCCs induced tube formation in an angiogenesis assay in vitro. CONCLUSIONS: This is the first study evaluating the possible interactions of primary human ADSCs with human SCCs, pointing towards a doubtlessly increased oncological risk, which should not be neglected when considering a clinical use of isolated human ADSCs in skin regenerative therapies.