Magnetic resonance neurography detects diabetic neuropathy early and with Proximal Predominance

Abstract

ObjectiveThe aim of this work was to localize and quantify alterations of nerve microstructure in diabetic polyneuropathy (DPN) by magnetic resonance (MR) neurography with large anatomical coverage.MethodsPatients (N = 25) with mild‐to‐moderate (Neuropathy‐Symptom‐Score [NSS]/Neuropathy Deficit Score [NDS] 3.8 ± 0.3/2.6 ± 0.5) and patients (n = 10) with severe DPN (6.2 ± 0.6/7.4 ± 0.5) were compared to patients (n = 15) with diabetes but no DPN and to age‐/sex‐matched nondiabetic controls (n = 25). All subjects underwent MR neurography with large spatial coverage and high resolution from spinal nerve to ankle level: four slabs per leg, each with 35 axial slices (T2‐ and proton‐density–weighted two dimensional turbo‐spin‐echo sequences; voxel size: 0.4 × 0.3 × 3.5 mm3) and a three‐dimensional T2‐weighted sequence to cover spinal nerves and plexus. Nerve segmentation was performed on a total of 280 slices per subject. Nerve lesion voxels were determined independently from operator input by statistical classification against the nondiabetic cohort. At the site with highest lesion‐voxel burden, signal quantification was performed by calculating nerve proton spin density and T2 relaxation time.ResultsTotal burden of nerve lesion voxels was significantly increased in DPN (p = 0.003) with strong spatial predominance at thigh level, where average lesion voxel load was significantly higher in severe (57 ± 18.4; p = 0.0022) and in mild‐to‐moderate DPN (35 ± 4.0; p < 0.001) than in controls (18 ± 3.6). Signal quantification at the site of predominant lesion burden (thigh) revealed a significant increase of nerve proton spin density in severe (360 ± 22.9; p = 0.043) and in mild‐to‐moderate DPN (365 ± 15.2; p = 0.001) versus controls (288 ± 13.4), but not of T2 relaxation time (p = 0.49). Nerve proton spin density predicted severity of DPN with an odds ratio of 2.9 (95% confidence interval: 2.4–3.5; p < 0.001) per 100 proton spins.InterpretationIn DPN, the predominant site of microstructural nerve alteration is at the thigh level with a strong proximal‐to‐distal gradient. Nerve proton spin density at the thigh level is a novel quantitative imaging biomarker of early DPN and increases with neuropathy severity. Ann Neurol 2015;78:939–948

Posterior interosseous neuropathy

“…30–32 Recent neuroimaging studies of diabetic and neurofibromatosis-associated polyneuropathies have shown the disseminated multifocality of nerve lesions whose cumulation correlates with symptom severity. 33,34 A length-dependent radial mononeuropathy could first present with finger drop, as seen in our patients, before eventually proceeding to involve additional muscles. This was actually the case in 4 patients excluded from our study because their disease had progressed before the MRI to also involve more proximal muscles.…”

Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis

“…All participants were examined feet first, in supine position in a 3.0 Tesla MR scanner (Magnetom TIM‐TRIO, Siemens Healthineers, Erlangen, Germany), and a 15‐channel Transmit‐Receive knee‐coil (INVIVO, Gainesville, FL, USA) was positioned at the right distal thigh. The thigh was chosen as previous studies showed a strong predominance of nerve lesions at this anatomical location not only in ATTRv‐PNP but also in other PNPs 15,17,18 . Two axial three‐dimensional, gradient echo sequences with and without an off‐resonance saturation pulse (Gaussian envelop, duration = 9984 µsec, frequency offset = 1200 Hz) were carried out at the exact same slice position and with the following exact same sequence parameters:…”

“…MR neurography (MRN) can overcome some of the aforementioned diagnostic limitations by directly visualizing peripheral nerve lesions 11–21 . The quantitative MRN parameters, proton spin density ( ρ ) and apparent T2 relaxation time ( T2 app ), have previously proven their feasibility to detect subclinical and early nerve lesions as well as to differentiate between neuropathic patients and controls or even between different disease severities in several neuropathies 14–18 . However, the changes in macromolecular structures that underlie alterations in ρ and T2 app still need to be elucidated.…”

Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy

“…Therefore, MRN can play a key role in understanding the spatiotemporal distribution and propagation of microstructural nerve alterations in DPN and for early monitoring of microstructural effects of therapeutic interventions. 134 More recently, several variations of MRN sequences have been proposed, which can achieve both high resolution and good fat suppression on 3T scanners. 135 …”