Project title: How Diffusion changes within the Ulnar Nerve following Cubital Tunnel Release

Grant Holder: Ryckie Wade

Position: NIHR Academic Clinical Lecturer

Date of award

Jan 2022

Start date for research

Feb 2022

Date of report

March 2023

Grant Awarded (i.e. £10,000)

£10,000

Is this an interim, or final, report

Final

Summary of project/progress /findings (approx 300 words)

Cubital tunnel syndrome (CuTS) is the 2^nd most common compression neuropathy (~6% prevalence^1,2) which changes the architecture of the ulnar nerve^3,4, leading to demyelination, axonal loss and fibrosis^3,4. Surgery is the recommended treatment for CuTS but the health service lacks a reliable test for CuTS^5–8. Therefore, clinicians observe patients for a mean ~15 months before offering surgery and/or use electrodiagnostic tests which have a high false-negative rate^8,9. This diagnostic delay means that most patients develop muscle loss prior to surgery¹⁰ and 13% don’t benefit¹¹.

Diffusion-weighted magnetic resonance imaging (dMRI) characterises tissue microstructure and provides reproducible^12–15 proxy measures of nerve health which are sensitive to axon type, diameter, density, myelination and organisation^16–19. Our group has already shown that dMRI can differentiate healthy ulnar nerves from those affected by cubital tunnel syndrome²⁰, whereby patients with CuTS have a 6% lower fractional anisotropy and 23% higher radial diffusivity (Figure 1) than healthy controls.

Figure 1. Longitudinal (left) and axial (right) sections of a peripheral nerve. Diffusion of water in healthy nerves (blue) is bidirectional. In nerves subject to chronic compression (red), demyelination enables water to diffuse radially between axons and axonal loss means a net reduction in anisotropy.

The aim of this study was to ascertain how diffusion within the ulnar nerve changes following surgical decompression. The hypothesis is that after decompression, the ulnar nerve architecture would improve (with axonal regeneration, remyelination, etc) and so, diffusion would recover anisotropy.

Methods

To-date, we have recruited 17 patients with CuTS. Of these, 14 have undergone pre-operative dMRI followed by surgical decompression. Five have returned for their 3-month post-operative scan, 2 are lost to follow-up and the remainder have scans booked.

Results

Interim analyses of the available data indicates that anisotropy in the ulnar nerve recovers after surgical decompression. At just 3-months post-operatively, dMRI detects a mean improvement in anisotropy of 2% and a 9% reduction in radial diffusivity, which suggests the regeneration of neural structures¹⁹ and restoration of normal axoplasmic flow.

Figure 2. Raincloud plot showing that 3-months following surgical decompression, the fractional anisotropy within the ulnar nerve improves by a mean of 2% (CI 1-4%)

What is the relevance/value of this research to hand surgery:

By harnessing quantitative MRI metrics derived multiparametric scans of nerves and end organs (muscles, tendon and skin), we may be better able to diagnose and characterise CuTS. This may enable earlier diagnosis, predictions about who may benefit from certain treatments, and objective quantification of nerve & muscle recovery following treatment.

The NHS treats ~112,000 patients with nerve compression annually²¹. Most undergo electrophysiology but MRI is cheaper (NIHR Tariff: £389 vs £444), safe, pain-free, generates high-resolution structural images and quantifies tissue/organ function via diffusion, perfusion, spectroscopy, angiography, etc. In the long-term, switching to MRI could save the NHS ~£6.2million annually. 

If final report, please provide bullet point list of conclusions/important findings:

• At just 3-months post-operatively dMRI can detect microstructural changes in the ulnar nerve which suggests the regeneration of neural structures¹⁹ and restoration of axoplasmic flow.
• At 3-months after decompression, fractional anisotropy recovers a mean 2% (95% CI 1-4) and there is a 9% reduction in radial diffusivity.
• This adds to the evidence that multiparametric quantitative MRI may be a valuable tool for objective, reproducible and reliable quantification of nerve health and end-organ function.

Please list presentations based on work performed in this study

We plan to submit works to the BSSH, IFSSH, ISMRM and ASPN in 2024.

Please state what additional research this study has/is leading to

A substantial number of patients are still required to undergo postoperative imaging and we expect the final data/results to be available Q2 2024. This proof-of-concept work has provided data for a pilot study on multiparametric qMRI in CuTS, covering nerve and muscle dMRI, fat fractions and iron content. For this study, we have applied for further funding outlined below

Please list any further funding or grant applications (with outcome), which have resulted from the award of this grant

• NIHR i4i FAST (£50k) – awarded March 2023 for the project “Accelerating the acquisition of dMRI from the Upper Limb”
• The Radiological Research Trust Annual Award (£5k) – awarded January 2023 for the project “The Association between qMRI derived skeletal muscle fat fractions and histological ground truth in patients with CuTS”
• Application to the Academy of Medical Sciences Clinical Lecturer Starter Grant (30k) in March 2023 – outcome pending.

How has this grant awards helped your career development?

This grant has enabled me to gather new skills in qMRI, create new collaborations with clinicians, MR physicists, pathologists and radiologists. It has helped me to better understand the research landscape and needs of patients with CuTS. With data derived from this study, I have been awarded several postdoctoral grants and together, these will form the foundation of an Advanced Fellowship application.