Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes.

BACKGROUND: Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC). METHODS: 3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data. RESULTS: The sciatic nerve's MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r = - 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve's MTR peroneal NCV (r = - 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016). CONCLUSIONS: Lower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D. TRIAL REGISTRATION: https://classic. CLINICALTRIALS: gov/ct2/show/NCT03022721 . 16 January 2017. RELEVANCE STATEMENT: Magnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes. KEY POINTS: • Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients. • Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes. • Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.

Phase angle of bioelectrical impedance analysis as an indicator for diabetic polyneuropathy in type 2 diabetes mellitus.

CONTEXT: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routine leading to increased morbidity and mortality. OBJECTIVE: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory and physical markers of DPN to evaluate PhA as possible diagnostic method for DPN. MATERIALS AND METHODS: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), amongst which 63 had DPN. The PhA was calculated from multi-frequency BIA. Nerve conduction studies (NCS), quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography (MRN) to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed. RESULTS: T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, p = 0.007, + 6.1%) and healthy controls (6.18 ± 0.08, p < 0.001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (ß=0.28; ß=0.31, p < 0.001) and tibial nerves (ß=0.28; ß=0.32, p < 0.001), Z-scores of QST (thermal detection ß=0.30, p < 0.05) and the FA (ß=0.60, p < 0.001). ROC analysis showed similar performance of PhA in comparison to mentioned diagnostic methods. CONCLUSION: The study shows that PhA is in comparison to other test systems used, at least an equally good and much easier to handle, investigator independent marker for detection of DPN.

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.

Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.

INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A­fibers (δ) and unmyelinated C­fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN. METHODS: A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (Ktrans), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp). RESULTS: The Ktrans (HC 0.031 min-1 ± 0.009, T2D 0.043 min-1 ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z­scores of thermal and mechanical detection correlated with Ktrans (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z­scores of thermal pain and Vp (r = -0.57; p = 0.015) correlated negatively. DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.

A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes. METHODS: Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST. RESULTS: Objective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve's FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm2; p=0.011) across the four phenotypes. Further, MH and SL were associated with a lower sciatic FA (MH unstandardised regression coefficient [B]=-0.048 [95% CI -0.091, -0.006], p=0.027; SL B=-0.062 [95% CI -0.103, -0.020], p=0.004) and CSA (MH ß=4.3 [95% CI 0.5, 8.0], p=0.028; SL B=4.0 [95% CI 0.4, 7.7], p=0.032) in a multivariable regression analysis. The sciatic FA correlated negatively with the sciatic CSA (r=-0.35, p=0.002) and markers of microvascular damage (high-sensitivity troponin T, urine albumin/creatinine ratio). CONCLUSIONS/INTERPRETATION: The most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN. TRIAL REGISTRATION: ClinicalTrials.gov NCT03022721.

Insulin Resistance Is Associated With Reduced Capillary Permeability of Thigh Muscles in Patients With Type 2 Diabetes.

CONTEXT: Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals. OBJECTIVE: The aim of this study was to demonstrate the feasibility of a noninvasive assessment of human muscle microcirculation via dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of skeletal muscle in patients with type 2 diabetes (T2D). METHODS: A total of 56 participants (46 with T2D, 10 healthy controls [HC]) underwent DCE-MRI of the right thigh at 3 Tesla. The constant of the musculature's microvascular permeability (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) were calculated. RESULTS: In T2D patients, skeletal muscle Ktrans was lower (HC 0.0677 ± 0.002 min-1, T2D 0.0664 ± 0.002 min-1; P = 0.042) while the homeostasis model assessment (HOMA) index was higher in patients with T2D compared to HC (HC 2.72 ± 2.2, T2D 6.11 ± 6.2; P = .011). In T2D, Ktrans correlated negatively with insulin (r = -0.39, P = .018) and HOMA index (r = -0.38, P = .020). CONCLUSION: The results signify that skeletal muscle DCE-MRI can be employed as a noninvasive technique for the assessment of muscle microcirculation in T2D. Our findings suggest that microvascular permeability of skeletal muscle is lowered in patients with T2D and that a decrease in microvascular permeability is associated with insulin resistance. These results are of interest with regard to the impact of muscle perfusion on diabetic complications such as diabetic sarcopenia.

Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes.

Background: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve's FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL). Materials and methods: Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage. Results: Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls (p<0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p<0.001 and r=0.6; p<0.001) and sural sensory NCV (r=0.50; p<0.001). Participants with reduced sciatic nerve´s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p<0.01 and r=0.3; p<0.01) and lower (r=0.5; p<0.001 and r=0.3; p=<0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p<0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve´s FA (r=-0.5; p<0.001 and r= -0.3, p= 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain. Conclusion: This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.

Fractal dynamics of individual mitochondrial oscillators measure local inter-mitochondrial coupling.

Mitochondrial inner membrane potentials in cardiomyocytes may oscillate in cycles of depolarization/repolarization when the mitochondrial network is exposed to metabolic or oxidative stress. The frequencies of such oscillations are dynamically changing while clusters of weakly coupled mitochondrial oscillators adjust to a common phase and frequency. Across the cardiac myocyte, the averaged signal of the mitochondrial population follows self-similar or fractal dynamics; however, fractal properties of individual mitochondrial oscillators have not yet been examined. We show that the largest synchronously oscillating cluster exhibits a fractal dimension, D, that is indicative of self-similar behavior with D=1.27±0.11, in contrast to the remaining network mitochondria whose fractal dimension is close to that of Brownian noise, D=1.58±0.10. We further demonstrate that fractal behavior is correlated with local coupling mechanisms, whereas it is only weakly linked to measures of functional connections between mitochondria. Our findings suggest that individual mitochondrial fractal dimensions may serve as a simple measure of local mitochondrial coupling.

Navigator-based slice tracking for kidney pCASL using spin-echo EPI acquisition.

PURPOSE: To apply a navigator-based slice-tracking method to prospectively compensate respiratory motion for kidney pseudo-continuous arterial spin labeling (pCASL), using spin-echo (SE) EPI acquisition. METHODS: A single gradient-echo slice selection and projection readout at the location of the diaphragm along the inferior-superior direction was applied as a navigator. Navigator acquisition and fat suppression were inserted before each transverse imaging slice of the readouts of a 2D-SE-EPI-based pCASL sequence. Motion information was calculated after exclusion of the signal saturation in the navigator signal caused by EPI excitations. The motion information was then used to directly adjust the slice positioning in real time. RESULTS: The respiratory motion from the navigator signal was calculated, and slice positioning was changed in real time based on the motion information. We could show that motion compensation reduces kidney movement, and that the coefficients of variation across renal perfusion values were significantly reduced when motion correction was applied. The average reduction of coefficients of variation was approximately 20%, resulting in a more accurate and detailed structure of the respective perfusion maps. CONCLUSIONS: This study demonstrates the feasibility of a navigator-based slice-tracking technique in kidney imaging with a SE-EPI readout pCASL sequence to reduce kidney motion.

Quantification and Proximal-to-Distal Distribution Pattern of Tibial Nerve Lesions in Relapsing-Remitting Multiple Sclerosis : Assessment by MR Neurography.

PURPOSE: Recent studies suggest an involvement of the peripheral nervous system (PNS) in multiple sclerosis (MS). Here, we characterize the proximal-to-distal distribution pattern of peripheral nerve lesions in relapsing-remitting MS (RRMS) by quantitative magnetic resonance neurography (MRN). METHODS: A total of 35 patients with RRMS were prospectively included and underwent detailed neurologic and electrophysiologic examinations. Additionally, 30 age- and sex-matched healthy controls were recruited. 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was conducted using dual-echo 2­dimensional relaxometry sequences with spectral fat saturation. Quantification of PNS involvement was performed by evaluating microstructural (proton spin density (ρ), T2-relaxation time (T2app)), and morphometric (cross-sectional area, CSA) MRN markers in every axial slice. RESULTS: In patients with RRMS, tibial nerve lesions at the thigh and the lower leg were characterized by a decrease in T2app and an increase in ρ compared to controls (T2app thigh: p < 0.0001, T2app lower leg: p = 0.0040; ρ thigh: p < 0.0001; ρ lower leg: p = 0.0098). An additional increase in nerve CSA was only detectable at the thigh, while the semi-quantitative marker T2w-signal was not altered in RRMS in both locations. A slight proximal-to-distal gradient was observed for T2app and T2-signal, but not for ρ. CONCLUSION: PNS involvement in RRMS is characterized by a decrease in T2app and an increase in ρ, occurring with proximal predominance at the thigh and the lower leg. Our results indicate microstructural alterations in the extracellular matrix of peripheral nerves in RRMS and may contribute to a better understanding of the pathophysiologic relevance of PNS involvement.

Diametrical Effects of Glucose Levels on Microvascular Permeability of Peripheral Nerves in Patients With Type 2 Diabetes With and Without Diabetic Neuropathy.

Clinical studies investigating the benefit of glucose control on the progression of diabetic neuropathy (DN) have come to controversial results in patients with type 2 diabetes (T2D). This study aimed to assess associations of HbA1c levels with parameters of nerve perfusion in patients with T2D with and without DN using dynamic contrast-enhanced magnetic resonance neurography (DCE-MRN) at 3 Tesla. A total of 58 patients with T2D (20 with DN and 38 without DN) took part in this cross-sectional single-center study. Groups were matched for age, BMI, HbA1c, duration of T2D, and renal function. All patients underwent DCE-MRN with subsequent electrophysiologic and serologic testing. The extended Tofts model was used to quantify the sciatic nerve's microvascular permeability (Ktrans), volume fraction of the extracapillary extracellular space, and volume fraction of the plasma space. As a main result, we found that Ktrans correlated positively with HbA1c in patients with DN, while a negative correlation between the two parameters was found in patients without DN. Our results indicate that the effect of glucose control on the capillary permeability of peripheral nerves differs between patients with T2D with and without DN.

Endodontic working length measurements of premolars and molars in high-resolution dental MRI: a clinical pilot study for assessment of reliability and accuracy.

OBJECTIVES: To prospectively assess the reliability and accuracy of high-resolution, dental MRI (dMRI) for endodontic working length (WL) measurements of premolars and molars under clinical conditions. MATERIALS AND METHODS: Three-Tesla dMRI was performed in 9 subjects who also had undergone cone-beam computed tomography (CBCT) (mean age: 47 ± 13.5 years). A total of 34 root canals from 12 molars (4/8, upper/lower jaw; 22 root canals) and 11 premolars (2/9 upper/lower jaw; 12 root canals) were included. CBCT and dMRI datasets were reconstructed to visualize the root canal in one single slice. Subsequently, two radiologists measured the root canal lengths in both modalities twice in blinded fashion. Reliability and accuracy for both modalities were assessed using intraclass correlation coefficients (ICCs) and Bland-Altman analysis, respectively. RESULTS: Reliability (intra-rater I/II; inter-rater) of dental MRI measurements was excellent and comparable to CBCT for premolars (0.993/0.900; 0.958 vs. 0.993/0.956; 0.951) and for molars (0.978/0.995; 0.986 vs. 0.992/0.996; 0.989). Bland-Altman analysis revealed a mean underestimation/bias (95% confidence interval) of dMRI measurements of 0.8 (- 1.44/3.05) mm for premolars and 0.4 (- 1.55/2.39) mm for molars. In up to 59% of the cases, the accuracy of dMRI for WL measurements was within the underestimation margin of 0 to 2 mm short of the apical foramen AF. CONCLUSIONS: In vivo demonstration and measurement of WL are feasible using dMRI. The reliability of measurements is high and equivalent to CBCT. Nonetheless, due to lower spatial resolution and longer acquisition time, the accuracy of dMRI is inferior to CBCT, impeding its current use for clinical treatment planning. CLINICAL RELEVANCE: dMRI is a promising radiation-free imaging technique. Its reliability for endodontic working length measurements is high, but its accuracy is not satisfactory enough yet.

Methodologies and MR Parameters in Quantitative Magnetic Resonance Neurography: A Scoping Review Protocol.

Magnetic resonance neurography (MRN), the MR imaging of peripheral nerves, is clinically used for assessing and monitoring peripheral neuropathies based on qualitative, weighted MR imaging. Recently, quantitative MRN has been increasingly reported with various MR parameters as potential biomarkers. An evidence synthesis mapping the available methodologies and normative values of quantitative MRN of human peripheral nerves, independent of the anatomical location and type of neuropathy, is currently unavailable and would likely benefit this young field of research. Therefore, the proposed scoping review will include peer-reviewed literature describing methodologies and normative values of quantitative MRN of human peripheral nerves. The literature search will include the databases MEDLINE (PubMed), EMBASE (Ovid), Web of Science, and Scopus. At least two independent reviewers will screen the titles and abstracts against the inclusion criteria. Potential studies will then be screened in full against the inclusion criteria by two or more independent reviewers. From all eligible studies, data will be extracted by two or more independent reviewers and presented in a diagrammatic or tabular form, separated by MR parameter and accompanied by a narrative summary. The reporting will follow the guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Upon completion, the scoping review will provide a map of the available literature, identify possible gaps, and inform on possible future research. SCOPING REVIEW REGISTRATION: Open Science Framework 9P3ZM.

Diabetic neuropathy is a generalized phenomenon with impact on hand functional performance and quality of life.

BACKGROUND AND PURPOSE: Diabetic sensorimotor peripheral neuropathy is usually considered to affect predominantly the lower limbs (LL-N), whereas the impact of upper limb neuropathy (UL-N) on hand functional performance and quality of life (QoL) has not been evaluated systematically. This study aims to investigate the prevalence and characteristics of UL-N and its functional and psychosocial consequences in type 2 diabetes. METHODS: Individuals with type 2 diabetes (n = 141) and an age- and sex-matched control group (n = 73) underwent comprehensive assessment of neuropathy, hand functional performance, and psychosocial status. RESULTS: The prevalence of UL-N was 30.5% in patients with diabetes and that of LL-N was 49.6%, with 25.5% exhibiting both. Patients with diabetes showed similar sensory phenotype regarding both large and small fiber functions in hands and feet. Patients with UL-N showed reduced manual dexterity, but normal hand grip force. Additionally, there was a correlation between reduced dexterity and sensory deficits. Patients with UL-N had reduced estimates of psychosocial health including health-related QoL compared to control subjects and patients without UL-N. UL-N correlated with the severity of LL-N, but not with duration of diabetes, glycemia, age, or sex. CONCLUSIONS: This study points to a substantial prevalence of UL-N in type 2 diabetes. The sensory phenotype of patients with UL-N was similar to LL-N and was characterized by loss of sensory function. Our study demonstrated an association of UL-N with impaired manual dexterity and reduced health-related QoL. Thus, upper limb sensorimotor functions should be assessed early in patients with diabetes.

Troponin T Is Negatively Associated With 3 Tesla Magnetic Resonance Peripheral Nerve Perfusion in Type 2 Diabetes.

Objective: The pathogenesis of diabetic polyneuropathy (DN) is poorly understood and given the increasing prevalence of DN, there is a need for clinical or imaging biomarkers that quantify structural and functional nerve damage. While clinical studies have found evidence of an association between elevated levels of troponin T (hsTNT) and N-terminal pro brain natriuretic peptide (proBNP) with microvascular compromise in type 2 diabetes (T2D), their implication in mirroring DN nerve perfusion changes remains unclear. The objective of this study was, therefore, to investigate whether hsTNT and proBNP assays are associated with MRI nerve perfusion in T2D. Methods: In this prospective cross-sectional single-center case-control study, 56 participants (44 with T2D, 12 healthy control subjects) consented to undergo magnetic resonance neurography (MRN) including dynamic contrast-enhanced (DCE) perfusion imaging of the right leg. Using the extended Tofts model, primary outcome parameters that were quantified are the sciatic nerve's microvascular permeability (Ktrans), the extravascular extracellular volume fraction (ve), and the plasma volume fraction (vp), as well as hsTNT and proBNP values from serological workup. Further secondary outcomes were clinical, serological, and electrophysiological findings. Results: In T2D patients, hsTNT was negatively correlated with Ktrans (r=-0.38; p=0.012) and ve (r=-0.30; p=0.048) but not with vp (r=-0.16; p=0.294). HsTNT, Ktrans, and ve were correlated with peroneal nerve conduction velocities (NCVs; r=-0.44; p=0.006, r=0.42; p=0.008, r=0.39; p=0.014), and tibial NCVs (r=-0.38;p=0.022, r=0.33; p=0.048, r=0.37; p=0.025). No such correlations were found for proBNP. Conclusions: This study is the first to find that hsTNT is correlated with a decrease of microvascular permeability and a reduced extravascular extracellular volume fraction of nerves in patients with T2D. The results indicate that hsTNT may serve as a potential marker for the assessment of nerve perfusion in future studies on DN.

Sciatic nerve microvascular permeability in type 2 diabetes decreased in patients with neuropathy.

OBJECTIVES: Clinical and histological studies have found evidence that nerve ischemia is a major contributor to diabetic neuropathy (DN) in type 2 diabetes (T2D). The aim of this study was to investigate peripheral nerve microvascular permeability using dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) to analyze potential correlations with clinical, electrophysiological, and demographic data. METHODS: Sixty-five patients (35/30 with/without DN) and 10 controls matched for age and body mass index (BMI) underwent DCE MRN of the distal sciatic nerve with an axial T1-weighted sequence. Microvascular permeability (Ktrans ), plasma volume fraction (vp ), and extravascular extracellular volume fraction (ve ) were determined with the extended Tofts model, and subsequently correlated with clinical data. RESULTS: Ktrans and ve were lower in T2D patients with DN compared to patients without DN (0.037 min-1 ± 0.010 vs. 0.046 min-1 ± 0.014; p = 0.011, and 2.35% ± 3.87 vs. 5.11% ± 5.53; p = 0.003, respectively). In individuals with T2D, Ktrans correlated positively with tibial, peroneal, and sural NCVs (r = 0.42; 95%CI = 0.18 to 0.61, 0.50; 95%CI = 0.29 to 0.67, and 0.44; 95%CI = 0.19 to 0.63, respectively), with tibial and peroneal CMAPs (r = 0.27; 95%CI = 0.01 to 0.49 and r = 0.32; 95%CI = 0.07 to 0.53), and with the BMI (r = 0.47; 95%CI = 0.25 to 0.64). Negative correlations were found with the neuropathy deficit score (r = -0.40; 95%CI = -0.60 to -0.16) and age (r = -0.51; 95%CI = -0.67 to -0.31). No such correlations were found for vp . CONCLUSION: This study is the first to find associations of MR nerve perfusion parameters with clinical and electrophysiological parameters related to DN in T2D. The results indicate that a decrease in microvascular permeability but not plasma volume may result in nerve ischemia that subsequently causes demyelination.

Brain tumor classification of virtual NMR voxels based on realistic blood vessel-induced spin dephasing using support vector machines.

Remodeling of tissue microvasculature commonly promotes neoplastic growth; however, there is no imaging modality in oncology yet that noninvasively quantifies microvascular changes in clinical routine. Although blood capillaries cannot be resolved in typical magnetic resonance imaging (MRI) measurements, their geometry and distribution influence the integral nuclear magnetic resonance (NMR) signal from each macroscopic MRI voxel. We have numerically simulated the expected transverse relaxation in NMR voxels with different dimensions based on the realistic microvasculature in healthy and tumor-bearing mouse brains (U87 and GL261 glioblastoma). The 3D capillary structure in entire, undissected brains was acquired using light sheet fluorescence microscopy to produce large datasets of the highly resolved cerebrovasculature. Using this data, we trained support vector machines to classify virtual NMR voxels with different dimensions based on the simulated spin dephasing accountable to field inhomogeneities caused by the underlying vasculature. In prediction tests with previously blinded virtual voxels from healthy brain tissue and GL261 tumors, stable classification accuracies above 95% were reached. Our results indicate that high classification accuracies can be stably attained with achievable training set sizes and that larger MRI voxels facilitated increasingly successful classifications, even with small training datasets. We were able to prove that, theoretically, the transverse relaxation process can be harnessed to learn endogenous contrasts for single voxel tissue type classifications on tailored MRI acquisitions. If translatable to experimental MRI, this may augment diagnostic imaging in oncology with automated voxel-by-voxel signal interpretation to detect vascular pathologies.

Characterization and quantification of alcohol-related polyneuropathy by magnetic resonance neurography.

BACKGROUND: We characterized and quantified peripheral nerve damage in alcohol-dependent patients (ADP) by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. METHODS: Thirty-one adult patients with a history of excessive alcohol consumption and age-/sex-matched healthy controls were prospectively examined. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into ADP with alcohol-related polyneuropathy (ALN) and without ALN (Non-ALN). 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was performed using dual-echo 2-dimensional relaxometry sequences with spectral fat saturation. Detailed quantification of nerve injury by morphometric (cross-sectional area [CSA]) and microstructural MRN markers (proton spin density [ρ], apparent T2-relaxation-time [T2app ]) was conducted in all study participants. RESULTS: MRN detected nerve damage in ADP with and without ALN. A proximal-to-distal gradient was identified for nerve T2-weighted (T2w)-signal and T2app in ADP, indicating a proximal predominance of nerve lesions. While all MRN markers differentiated significantly between ADP and controls, microstructural markers were able to additionally differentiate between subgroups: tibial nerve ρ at thigh level was increased in ALN (p < 0.0001) and in Non-ALN (p = 0.0052) versus controls, and T2app was higher in ALN versus controls (p < 0.0001) and also in ALN versus Non-ALN (p = 0.0214). T2w-signal and CSA were only higher in ALN versus controls. CONCLUSIONS: MRN detects and quantifies peripheral nerve damage in ADP in vivo even in the absence of clinically overt ALN. Microstructural markers (T2app , ρ) are most suitable for differentiating between ADP with and without manifest ALN, and may help to elucidate the underlying pathomechanism in ALN.

Quantitative assessment of contrast-enhancement patterns of the healthy dental pulp by magnetic resonance imaging: A prospective in vivo study.

AIM: This prospective in vivo study aimed to optimize the assessment of pulpal contrast-enhancement (PCE) on dental magnetic resonance imaging (dMRI) and investigate physiological PCE patterns. METHODOLOGY: In 70 study participants, 1585 healthy teeth were examined using 3-Tesla dMRI before and after contrast agent administration. For all teeth, the quotient of post- and pre-contrast pulp signal intensity (Q-PSI) was calculated to quantify PCE. First, pulp chambers were analysed in 10 participants to compare the coefficient of variation of mean versus maximum Q-PSI values (Q-PSImean versus Q-PSImax ). Second, dynamic PCE was evaluated in 10 subjects to optimize the time interval between contrast agent application and image acquisition. Finally, 50 participants (age groups: 20-29, 30-39, 40-49, 50-59 and 60-69 years) were examined to analyse age, gender, tooth types and maxilla versus mandible as independent factors of PCE. Statistical analysis was performed using Wilcoxon signed rank test and linear mixed models. RESULTS: PCE assessment based on Q-PSImax was associated with a significantly smaller coefficient of variation compared with Q-PSImean , with median values of 0.17 versus 0.21 (p = .002). Analysis of dynamic PCE revealed an optimal timing interval for image acquisition 4 min after contrast media application. No significant differences in PCE were observed by comparing age groups, female versus male participants and maxillary versus mandibular teeth (p > .05). Differences between tooth types were small (median Q-PSImax values of 2.52/2.32/2.30/2.20 for molars/premolars/canines/incisors) but significant (p < .05), except for the comparison of canines versus premolars (p = .80). CONCLUSIONS: PCE in dMRI was a stable intra-individual marker with only minor differences between different tooth types, thus forming an important basis for intra-individual controls when assessing teeth with suspected endodontic pathosis. Furthermore, it was demonstrated that PCE is independent of age, gender and jaw type. These findings indicate that dMRI-based PCE analysis could be a valuable diagnostic tool for the identification of various pulp diseases in future patient studies.