Microstructure Imaging of Nerve Regeneration Network
The clinical problem: Nerve injuries can be debilitating for patients, resulting in long term loss of sensation and power and control of movement and the possibility of chronic pain. A variety of microsurgical approaches are used to repair damaged nerves, however there are only clinical surrogates available to assess and quantifying the speed and extent of nerve regeneration following injury. Current techniques tend to be limited to indirect measures of response to mechanical stimulation (a clinical sign known as Tinel’s sign), and predictions based on crude estimates of neuronal growth rate.
The aim of the project: This project aims to develop a cutting-edge microstructure imaging techniques to visualize in-vivo and non-invasively the growth of the neurons in the peripheral nerve system (PNS). Microstructure imaging techniques involve a combination of Diffusion MRI, mathematical models of nerve tissue and computational methods for sequence optimisation and parameter estimation. They can quantify neuronal regeneration using microstructure indices such as axonal diameter, density and orientation.
The proposed methodology: The project will firstly develop novel diffusion MRI techniques to study PNS tissue microstructure. For this it will develop a mathematical model of PNS tissue and then use sophisticated computational methods to optimize diffusion MRI sequences for sensitivity to the parameters of that model, such as axon diameter and density, which are crucial when assessing nerve damage and regeneration. The project will then apply these new techniques of microstructure imaging to a group of patients with upper limb peripheral nerve injuries under the care of the Peripheral Nerve Injury Unit of the Royal National Orthopaedic Hospital (RNOH). This will allow investigation of how axonal properties change throughout the process of regeneration and investigate the characteristics of neuronal regeneration. Further, the study will correlate these imaging findings with clinical markers and relate these to the functional ability of the arm, and estimate conduction delay, the key parameter that links microstructure and nerve function. Finally, it will evaluate different methods for nerve regeneration and repair.
Feasibility: Previous research has shown that Diffusion MRI of the PNS can be done with very good quality. Furthermore, we have shown recently in simulation (Drobnjak et al MRM 2015) and experimentally (Shrestha et al ISMRM 2014) that clinical scanner can image the sizes of axon diameters present in PNS.
Impact: Novel methodology will make a strong impact in monitoring and quantifying the extent of nerve regeneration following injury. That can lead to improved surgery performance and improved rehabilitation methods. Furthermore, understanding the nerve regeneration networks will contribute in developing better methods for nerve regeneration and repair.