Objectives
To evaluate whether magnetic resonance imaging (MRI) can serve as an alternative diagnostic tool to the “gold standard” cone-beam computed tomography (CBCT) in 3D cephalometric analysis.
...Methods
In this prospective feasibility study, 12 patients (8 males, 4 females; mean age ± SD, 26.1 years ± 6.6) underwent 3D MRI and CBCT before orthognathic surgery. 3D cephalometric analysis was performed twice by two independent observers on both modalities. For each dataset, 27 cephalometric landmarks were defined from which 35 measurements (17 angles, 18 distances) were calculated. Statistical analyses included the calculation of Euclidean distances, intraclass correlation coefficients (ICCs), Bland-Altman analysis, and equivalence testing (linear mixed effects model) with a predefined equivalence margin of ± 1°/1 mm.
Results
Analysis of reliability for CBCT vs. MRI (intra-rater I/intra-rater II/inter-rater) revealed Euclidean distances of 0.86/0.86/0.98 mm vs. 0.93/0.99/1.10 mm for landmarks, ICCs of 0.990/0.980/0.986 vs. 0.982/0.978/0.980 for angles, and ICCs of 0.992/0.988/0.989 vs. 0.991/0.985/0.988 for distances. Bland-Altman analysis showed high levels of agreement between CBCT and MRI with bias values (95% levels of agreement) of 0.03° (− 1.49; 1.54) for angles and 0.02 mm (− 1.44; 1.47) for distances. In the linear mixed effects model, the mean values of CBCT and MRI measurements were equivalent.
Conclusion
This feasibility study indicates that MRI enables reliable 3D cephalometric analysis with excellent agreement to corresponding measurements on CBCT. Thus, MRI could serve as a non-ionizing alternative to CBCT for treatment planning and monitoring in orthodontics as well as oral and maxillofacial surgery.
Key Points
• Clinically established 3D cephalometric measurements performed on MRI are highly reliable and show an excellent agreement with CBCT (gold standard).
• The MRI technique applied in this study could be used as a non-ionizing diagnostic tool in orthodontics as well as oral and maxillofacial surgery.
• Since most patients benefiting from 3D cephalometry are young in age, the use of MRI could substantially contribute to radiation protection and open up new possibilities for treatment monitoring.
Objectives
To evaluate the accuracy and reliability of dental MRI for static guided implant surgery planning.
Materials and methods
In this prospective study, a 0.4-mm isotropic, artifact-suppressed, ...3T MRI protocol was used for implant planning and surgical guide production in participants in need of dental implants. Two dentists decided on treatment plan. Surgical guides were placed intraorally during a subsequent reference cone beam computed tomography (CBCT) scan. Inter-rater and inter-modality agreement were assessed by Cohen’s kappa. For each participant, dental MRI and CBCT datasets were co-registered to determine three-dimensional and angular deviations between planned and surgically guided implant positions.
Results
Forty-five implants among 30 study participants were planned and evaluated (17 women, 13 men, mean age 56.9 ± 13.1 years). Inter-rater agreement (mean κ 0.814; range 0.704–0.927) and inter-modality agreement (mean κ 0.879; range 0.782–0.901) were both excellent for the dental MRI-based treatment plans. Mean three-dimensional deviations were 1.1 ± 0.7 (entry point) and 1.3 ± 0.7 mm (apex). Mean angular deviation was 2.4 ± 1.5°. CBCT-based adjustments of MRI plans were necessary for implant position in 29.5% and for implant axis in 6.8% of all implant sites. Changes were larger in the group with shortened dental arches compared with those for tooth gaps. Except for one implant site, all guides were suitable for clinical use.
Conclusion
This feasibility study indicates that dental MRI is reliable and sufficiently accurate for surgical guide production. Nevertheless, more studies are needed to increase its accuracy before it can be used for implant planning outside clinical trials.
Key Points
• An excellent reliability for the dental MRI-based treatment plans as well as agreement between dental MRI-based and CBCT-based (reference standard) decisions were noted.
• Ideal implant position was not reached in all cases by dental MRI plans.
• For all but one implant site surgical guides derived from dental MRI were sufficiently accurate to perform implant placement (mean three-dimensional deviations were 1.1 ± 0.7 (entry point) and 1.3 ± 0.7 mm (apex); mean angular deviation was 2.4 ± 1.5°).
Aims/hypothesis
The individual risk of progression of diabetic peripheral neuropathy is difficult to predict for each individual. Mutations in proteins that are responsible for the process of ...myelination are known to cause neurodegeneration and display alteration in experimental models of diabetic neuropathy. In a prospective observational human pilot study, we investigated myelin-specific circulating mRNA targets, which have been identified in vitro, for their capacity in the diagnosis and prediction of diabetic neuropathy. The most promising candidate was tested against the recently established biomarker of neural damage, neurofilament light chain protein.
Methods
Schwann cells were cultured under high-glucose conditions and mRNAs of various myelin-specific genes were screened intra- and extracellularly. Ninety-two participants with type 2 diabetes and 30 control participants were enrolled and evaluated for peripheral neuropathy using neuropathy deficit scores, neuropathy symptom scores and nerve conduction studies as well as quantitative sensory testing at baseline and after 12/24 months of a follow-up period. Magnetic resonance neurography of the sciatic nerve was performed in 37 individuals. Neurofilament light chain protein and four myelin-specific mRNA transcripts derived from in vitro screenings were measured in the serum of all participants. The results were tested for associations with specific neuropathic deficits, fractional anisotropy and the progression of neuropathic deficits at baseline and after 12 and 24 months.
Results
In neuronal Schwann cells and human nerve sections, myelin protein zero was identified as the strongest candidate for a biomarker study. Circulating mRNA of myelin protein zero was decreased significantly in participants with diabetic neuropathy (
p
< 0.001), whereas neurofilament light chain protein showed increased levels in participants with diabetic neuropathy (
p
< 0.05). Both variables were linked to altered electrophysiology, fractional anisotropy and quantitative sensory testing. In a receiver-operating characteristic curve analysis myelin protein zero improved the diagnostic performance significantly in combination with a standard model (diabetes duration, age, BMI, HbA
1c
) from an AUC of 0.681 to 0.836 for the detection of diabetic peripheral neuropathy. A follow-up study revealed that increased neurofilament light chain was associated with the development of a hyperalgesic phenotype (
p
< 0.05), whereas decreased myelin protein zero predicted hypoalgesia (
p
< 0.001) and progressive loss of nerve function 24 months in advance (HR of 6.519).
Conclusions/interpretation
This study introduces a dynamic and non-invasive assessment strategy for the underlying pathogenesis of diabetic peripheral neuropathy. The diagnosis of axonal degeneration, associated with hyperalgesia, and demyelination, linked to hypoalgesia, could benefit from the usage of neurofilament light chain protein and circulating mRNA of myelin protein zero as potential biomarkers.
Graphical abstract
Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been ...recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve's fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve's FA (
= -0.52,
< 0.001), with a closer correlation in DN patients (
= -0.66,
< 0.001). hsTNT further correlated positively with the neuropathy disability score (
= 0.39,
= 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (
= -0.65,
< 0.001) and tibial NCVs (
= -0.44,
= 0.002) and amplitudes (
= -0.53,
< 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.
Studies on magnetic resonance neurography (MRN) in diabetic polyneuropathy (DPN) have found proximal sciatic nerve lesions. The aim of this study was to evaluate the functional relevance of sciatic ...nerve lesions in DPN, with the expectation of correlations with the impairment of large-fiber function. Sixty-one patients with type 2 diabetes (48 with and 13 without DPN) and 12 control subjects were enrolled and underwent MRN, quantitative sensory testing, and electrophysiological examinations. There were differences in mechanical detection (Aβ fibers) and mechanical pain (Aδ fibers) but not in thermal pain and thermal detection clusters (C fibers) among the groups. Lesion load correlated with lower Aα-, Aβ-, and Aδ-fiber but not with C-fiber function in all participants. Patients with lower function showed a higher load of nerve lesions than patients with elevated function or no measurable deficit despite apparent DPN. Longer diabetes duration was associated with higher lesion load in patients with DPN, suggesting that nerve lesions in DPN may accumulate over time and become clinically relevant once a critical amount of nerve fascicles is affected. Moreover, MRN is an objective method for determining lower function mainly in medium and large fibers in DPN.
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.
Objective
To detect and quantify peripheral nerve lesions in multiple sclerosis (MS) by magnetic resonance neurography (MRN).
Methods
Thirty‐six patients diagnosed with MS based on the 2010 McDonald ...criteria (34 with the relapsing–remitting form, 2 with clinically isolated syndrome) with and without disease‐modifying treatment were compared to 35 healthy age‐/sex‐matched volunteers. All patients underwent detailed neurological and electrophysiological examinations. Three Tesla MRN with large anatomical coverage of both legs and the lumbosacral plexus was performed by using 2‐dimensional (2D) fat‐saturated, T2‐weighted (T2w) and dual echo turbo spin echo sequences as well as a 3D T2‐weighted, fat‐saturated SPACE sequence. Besides qualitative visual nerve assessment, a T2w signal quantification was performed by calculation of proton spin density and T2 relaxation time. Nerve diameter was measured as a morphometric criterion.
Results
T2w hyperintense nerve lesions were detectable in all MS patients, with a mean lesion number at thigh level of 151.5 ± 5.7 versus 19.1 ± 2.4 in controls (p < 0.0001). Nerve proton spin density was higher in MS (tibial/peroneal: 371.8 ± 7.7/368.9 ± 8.2) versus controls (tibial/peroneal: 266.0 ± 11.0/276.8 ± 9.7, p < 0.0001). In contrast, T2 relaxation time was significantly higher in controls (tibial/peroneal: 82.0 ± 2.1/78.3 ± 1.7) versus MS (tibial/peroneal: 64.3 ± 1.0/61.2 ± 0.9, p < 0.0001). Proximal tibial and peroneal nerve caliber was higher in MS (tibial: 52.4 ± 2.1mm2, peroneal: 25.4 ± 1.3mm2) versus controls (tibial: 45.2 ± 1.4mm2, p < 0.0015; peroneal: 21.3 ± 0.7mm2, p = 0.0049).
Interpretation
Peripheral nerve lesions could be visualized and quantified in MS in vivo by high‐resolution MRN. Lesions are defined by an increase of proton spin density and a decrease of T2 relaxation time, indicating changes in the microstructural organization of the extracellular matrix in peripheral nerve tissue in MS. By showing involvement of the peripheral nervous system in MS, this proof‐of‐concept study may offer new insights into the pathophysiology and treatment of MS. Ann Neurol 2017;82:676–685
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 mm
2
;
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 β=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
Graphical Abstract
Objective
To visualize and quantify differences of microstructural nerve damage in distal symmetric diabetic neuropathy (DPN) between type 1 diabetes (T1D) and type 2 diabetes (T2D), and to detect ...correlations between neuropathic symptoms and serological risk factors.
Methods
Three‐tesla magnetic resonance neurography of the sciatic nerve was performed in 120 patients (T1D, n = 35; T2D, n = 85) with either DPN (n = 84) or no DPN (n = 36). Results were subsequently correlated with clinical, serological, and electrophysiological patient data.
Results
T2‐weighted (T2w)‐hyperintense lesions correlated negatively with tibial compound motor action potential (r = −0.58, p < 0.0001) and peroneal nerve conduction (r = 0.51, p = 0.0002), and positively with neuropathy disability score (NDS; r = −0.54, p < 0.0001), neuropathy symptom score (NSS; r = 0.52, p < 0.0001), and HbA1c level (r = 0.23, p = 0.014). T2w‐hypointense lesions correlated positively with NDS (r = 0.28, p = 0.002), NSS (r = 0.36, p < 0.0001), and serum triglycerides (r = 0.34, p = 0.0003), and negatively with serum high‐density lipoprotein (HDL; r = −0.48, p < 0.0001). For DPN in T1D, elevated values of T2w‐hyperintense lesions (19.67 ± 4.13% vs 12.49 ± 1.23%, p = 0.027) and HbA1c (8.74 ± 0.29% vs 7.11 ± 0.16%, p < 0.0001) were found when compared to T2D. For DPN in T2D, elevated T2w‐hypointense lesions (23.41 ± 2.69mm3 vs 11.43 ± 1.74mm3, p = 0.046) and triglycerides (220.70 ± 23.70mg/dl vs 106.60 ± 14.51mg/dl, p < 0.0001), and lower serum HDL (51.29 ± 3.02mg/dl vs 70.79 ± 4.65mg/dl, p < 0.0001) were found when compared to T1D.
Interpretation
The predominant type of nerve lesion in DPN differs between T1D and T2D. Correlations found between lesion type and serological parameters indicate that predominant nerve lesions in T1D are associated with poor glycemic control and loss of nerve conduction, whereas predominant lesions in T2D are associated with changes in lipid metabolism. These findings may be helpful for future studies on the underlying pathophysiological pathways and possible treatments for DPN in T1D and T2D. Ann Neurol 2018;83:588–598
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.
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