Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength

Daniel Schwarz,Sabine Heiland,Martin Bendszus,Peter P Nawroth,Asa S Hidmark,Manuel Fischer,Volker Sturm,Thomas Fleming,Rohini Kuner,Felix Sahm,David Milford,Nitin Agarwal,Ingrid Hausser,Michael O Breckwoldt

doi:10.1038/s41598-020-64585-1

Abstract

In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves’ fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.

Highlights

In vivo magnetic resonance neurography (MRN) of the peripheral nervous system (PNS) has recently identified distinct focal lesions within the sciatic nerve as a major hallmark of diabetic polyneuropathy (DPN) in both type 1 (T1D) and type 2 diabetic (T2D) patients[1,2,3]
The measurement of fractional anisotropy (FA), which reflects the spatial anisotropy in the extent of water molecule self-diffusion, was reduced within DPN nerve lesions, whereas apparent diffusion coefficient (ADC), which reflects the average extent of water molecule self-diffusion, was increased
The changes observed with respect to FA and ADC5,6 would again be suggestive of a change within the macromolecular compartment consistent with a loss of axons and myelin

Summary

Introduction

In vivo magnetic resonance neurography (MRN) of the peripheral nervous system (PNS) has recently identified distinct focal lesions within the sciatic nerve as a major hallmark of diabetic polyneuropathy (DPN) in both type 1 (T1D) and type 2 diabetic (T2D) patients[1,2,3] Such focal lesions have been reported to have a proximal predominance at thigh level and correlate closely to the degree of clinical severity. The objective of this study is to implement a novel multicontrast, ultra high field MRN approach to assess pathomorphological nerve changes at a very high resolution which can be applied to mice in vivo Such a non-invasive imaging toolbox may allow for detection of potential nerve lesions and distinct MR-signatures as correlate of experimental DPN and other neuropathic conditions. These findings can be compared to clinical, behavioural and histological parameters to eventually provide a better understanding of DPN-related nerve lesions

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